{"slug":"milk-thistle","name":"Milk Thistle (Silymarin)","csvName":"Milk thistle","rank":26,"rankingBasis":"Added from Patrick's pull list 2026-10-31 (keyword demand sheet); second PDF bundle","rankingSourceUrl":"","commonForms":["Standard silymarin extract","Silybin phytosome (silybin-phosphatidylcholine)","Other enhanced formulas (SMEDDS, micellar, water-soluble)"],"forms":[{"slug":"silymarin","label":"Standard silymarin extract","studyIds":["pmid-35061161","pmid-28098838","pmid-26595166","pmid-26642669","pmid-24317417","pmid-23835761","pmid-21315924","pmid-21865319","pmid-17913795","pmid-18566043","pmid-16221754","pmid-16432272","pmid-15666173","pmid-12885100","pmid-42264004","pmid-39567122","pmid-40493802","pmid-37774895","pmid-38529622","pmid-37457888","pmid-35708053","pmid-36557984","pmid-33587330","pmid-31706011","pmid-30668388","pmid-30904740","pmid-31185663","pmid-31420525","pmid-28952834","pmid-28958806","pmid-30416442","pmid-26152876","pmid-26222744","pmid-21802925","pmid-20942611","pmid-18428992","pmid-19226635","pmid-19470289","pmid-18048488","pmid-17692492","pmid-16275123","pmid-9008269","pmid-3398694","pmid-32654568","pmid-21948306","pmid-20405254","pmid-41729747","pmid-36985575","pmid-37342048","pmid-34695708","pmid-33237069","pmid-6870500","pmid-7283681"]},{"slug":"phytosome","label":"Silybin phytosome (silybin-phosphatidylcholine)","studyIds":["pmid-30635055","pmid-18054294","pmid-17077998","pmid-17315537","pmid-39861153","pmid-36775115","pmid-37506470","pmid-37645028","pmid-35890088","pmid-31923602","pmid-31207432","pmid-25375210","pmid-12748991","pmid-11529693","pmid-17348898","pmid-30935093"]},{"slug":"enhanced","label":"Other enhanced formulas (SMEDDS, micellar, water-soluble)","studyIds":["pmid-40733088","pmid-39204378","pmid-30108644","pmid-23072776","pmid-37695023","pmid-42497478","pmid-42956604","pmid-40685047","pmid-39370820","pmid-39418531","pmid-39498271","pmid-36719351","pmid-37506470","pmid-38093834","pmid-38139990","pmid-35460909","pmid-35560136","pmid-36178580","pmid-33246779","pmid-33257158","pmid-33616078","pmid-33925040","pmid-32337654","pmid-32473632","pmid-30643408","pmid-30766782","pmid-31207432","pmid-28503949","pmid-29162374","pmid-30176941","pmid-27436270","pmid-27575878","pmid-28778838","pmid-29026299","pmid-26556526","pmid-25735668","pmid-25848259","pmid-26543366","pmid-26770331","pmid-24766208","pmid-25149982","pmid-25375210","pmid-24039417","pmid-21111585","pmid-21549187","pmid-19863195","pmid-17328246","pmid-37964172","pmid-39079328","pmid-35300217","pmid-26669888","pmid-24495272","pmid-25956049","pmid-21666703","pmid-20523347","pmid-20621458","pmid-16527467","pmid-16687221","pmid-40992023","pmid-41722252","pmid-42660255","pmid-38794280","pmid-39344123","pmid-38144097","pmid-35214124","pmid-34944582","pmid-35300372","pmid-30448315","pmid-30502425","pmid-31052197","pmid-31715362","pmid-28553075","pmid-26674103","pmid-24008629","pmid-23851081","pmid-22343518","pmid-22530301","pmid-20332565","pmid-16356669"]}],"pairs":[{"anchor":"phytosome-vs-silymarin","a":"phytosome","b":"silymarin","aLabel":"Silybin phytosome (silybin-phosphatidylcholine)","bLabel":"Standard silymarin extract","studyIds":[],"evidence":{"grade":null,"basis":"no_data","rationale":"No relevant studies in the database for this question.","counts":{}}},{"anchor":"enhanced-vs-silymarin","a":"enhanced","b":"silymarin","aLabel":"Other enhanced formulas (SMEDDS, micellar, water-soluble)","bLabel":"Standard silymarin extract","studyIds":[],"evidence":{"grade":null,"basis":"no_data","rationale":"No relevant studies in the database for this question.","counts":{}}}],"studies":[{"id":"pmid-40733088","title":"Novel Micellar Formulation of Silymarin (Milk Thistle) with Enhanced Bioavailability in a Double-Blind, Randomized, Crossover Human Trial.","year":"2025","journal":"Pharmaceutics","pmid":"40733088","pmcid":null,"doi":"10.3390/pharmaceutics17070880","url":"https://pubmed.ncbi.nlm.nih.gov/40733088/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/40733088/","doiUrl":"https://doi.org/10.3390/pharmaceutics17070880","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12298458/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"randomized crossover (double-blind)","n":"16","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":true,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"the LipoMicel milk thistle formulation (LMM) exhibited significantly faster absorption, higher peak plasma concentrations, and greater overall exposure (AUC0–24) compared to the unformulated product, but it has a shorter mean residence time.","source":"fulltext","location":"Conclusions (section 5)","truncated":false},{"metric":"Tmax","text":"Tmax was 0.5 (95% CI: 0.5–4.0) hours for the micellar formulation versus 2.5 (95% CI: 0.5–8.0) hours","source":"fulltext","location":"Abstract; Results 3.2; Discussion","truncated":false},{"metric":"Cmax","text":"mean Cmax value of 66.1 ng/mL (95% CI: 4.9–127.3) for the 130 mg unformulated silymarin","source":"fulltext","location":"Discussion p.15","truncated":false},{"metric":"Comparison","text":"18.9-fold higher Cmax","source":"fulltext","location":"Table 3; Abstract","truncated":false},{"metric":"Comparison","text":"11.4-fold higher AUC0–24","source":"fulltext","location":"Table 3; Abstract; Results 3.2","truncated":false},{"metric":"Comparison","text":"Tmax was 0.5 ... hours for the micellar formulation versus 2.5","source":"fulltext","location":"Table 3; Abstract","truncated":false},{"metric":"Comparison","text":"standard formulation exhibited a significantly longer mean residence time","source":"fulltext","location":"Table 3; Abstract","truncated":false},{"metric":"Comparison","text":"the T½ levels were not significantly different between the standard formulation and LMM","source":"fulltext","location":"Table 3; Results 3.2","truncated":false}]},{"id":"pmid-39204378","title":"Nanocrystal Formulation to Enhance Oral Absorption of Silybin: Preparation, In Vitro Evaluations, and Pharmacokinetic Evaluations in Rats and Healthy Human Subjects.","year":"2024","journal":"Pharmaceutics","pmid":"39204378","pmcid":null,"doi":"10.3390/pharmaceutics16081033","url":"https://pubmed.ncbi.nlm.nih.gov/39204378/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/39204378/","doiUrl":"https://doi.org/10.3390/pharmaceutics16081033","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11359960/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"randomized crossover (human; two-period, single-dose); parallel groups in rats","n":"14 humans; rats NR in Methods (n = 5 per Fig. 8 legend)","formsStudiedRaw":"Milk thistle (silybin; HM40 nanocrystal formulation vs raw material)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In addition, the oral bioavailability of silybin from HM40 in rats and humans was enhanced by 2.61- and 1.51-fold, respectively, compared to that from the milk thistle raw material.","source":"fulltext","location":"Conclusions (p.15)","truncated":false},{"metric":"Comparison","text":"values of Cmax and AUCinf after oral administration of HM40 were 4.72- and 2.61-fold higher","source":"fulltext","location":"Table 2; Results 3.4","truncated":false},{"metric":"Comparison","text":"the MRT after oral administration of HM40 was significantly lower than that of milk thistle raw material","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"the MRT after the oral administration of the HM40 capsule was not significantly different from that of the reference capsule","source":"fulltext","location":"Results 3.5","truncated":false}]},{"id":"pmid-35061161","title":"Prediction of CYP-mediated silybin A-losartan pharmacokinetic interactions using physiological based pharmacokinetic modeling.","year":"2022","journal":"Journal of pharmacokinetics and pharmacodynamics","pmid":"35061161","pmcid":null,"doi":"10.1007/s10928-022-09804-0","url":"https://pubmed.ncbi.nlm.nih.gov/35061161/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/35061161/","doiUrl":"https://doi.org/10.1007/s10928-022-09804-0","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"other (PBPK modelling/simulation)","n":null,"formsStudiedRaw":"Milk thistle (silybin A)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Silybin A changed the AUC and Cmax of losartan in a genotype-dependent manner. The pharmacokinetic interactions between silybin A and losartan were minor when concomitantly administered at normal doses in genotypes CYP2C9*1/*1 and CYP2C9*1/*3. However, moderate interaction was found in CYP2C9*1/*2 genotype.","source":"fulltext","location":"Conclusion p.320","truncated":false},{"metric":"Comparison","text":"AUC and Cmax of losartan were increased 1.16 and 1.37 folds, respectively","source":"fulltext","location":"Abstract; Table 6","truncated":false},{"metric":"Comparison","text":"the losartan's AUC and Cmax were decreased by 0.01 folds, manifesting a moderate interaction","source":"fulltext","location":"Abstract; Table 6","truncated":false},{"metric":"Comparison","text":"Increase in AUC and Cmax by 0.873 and 0.294 folds, respectively in CYP2C9*1/*3","source":"fulltext","location":"Abstract; Table 6","truncated":false}]},{"id":"pmid-30635055","title":"Superior silybin bioavailability of silybin-phosphatidylcholine complex in oily-medium soft-gel capsules versus conventional silymarin tablets in healthy volunteers.","year":"2019","journal":"BMC pharmacology & toxicology","pmid":"30635055","pmcid":null,"doi":"10.1186/s40360-018-0280-8","url":"https://pubmed.ncbi.nlm.nih.gov/30635055/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/30635055/","doiUrl":"https://doi.org/10.1186/s40360-018-0280-8","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6330464/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"randomized crossover","n":"23 (24 enrolled)","formsStudiedRaw":"Milk thistle (silybin-phosphatidylcholine complex vs silymarin)","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The silybin–phosphatidylcholine complex in oily-medium soft-gel capsules seems to provide superior bioavailability. However, clinical studies must be performed to demonstrate its clinical relevance in the treatment of liver diseases.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"SIB peak plasma concentrations were 207.1 mg/L for SPC and 12.6 mg/L for SM tablets.","source":"fulltext","location":"Results p.3","truncated":false},{"metric":"Relative bioavailability","text":"SIB bioavailability is 9.6 times higher with SPC in oily-medium soft-gel capsules compared with conventional SM tablets","source":"fulltext","location":"Discussion p.4","truncated":false},{"metric":"Comparison","text":"All pharmacokinetic parameters differed significantly between formulations (P < 0.0001).","source":"fulltext","location":"Table 1; Results","truncated":false}]},{"id":"pmid-29273470","title":"Relative Bioavailability of Silybin A and Silybin B From 2 Multiconstituent Dietary Supplement Formulations Containing Milk Thistle Extract: A Single-dose Study.","year":"2018","journal":"Clinical therapeutics","pmid":"29273470","pmcid":null,"doi":"10.1016/j.clinthera.2017.11.013","url":"https://pubmed.ncbi.nlm.nih.gov/29273470/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/29273470/","doiUrl":"https://doi.org/10.1016/j.clinthera.2017.11.013","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6037411/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"randomized crossover (open-label)","n":"12","formsStudiedRaw":"Milk thistle extract (silymarin) in multi-ingredient supplements","formTags":[],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The IsaGenesis soft gel formulation provided substantially greater absorption and bioavailability of silybin A and silybin B relative to the powdered Product B supplement.","source":"fulltext","location":"Abstract (Implications)","truncated":false},{"metric":"Relative bioavailability","text":"284% (silybin A) and 334% (silybin B) greater than with the Product B formulation","source":"fulltext","location":"Table III","truncated":false},{"metric":"Comparison","text":"the absorption rate and extent, as indicated by mean the Cmax and mean plasma AUC, were significantly higher for the IsaGenesis soft gel formulation","source":"fulltext","location":"Abstract; Discussion p.111","truncated":false},{"metric":"Comparison","text":"The Tmax values were 2.0 hours for IsaGenesis versus 3.0 hours for Product B for both silybin isomers","source":"fulltext","location":"Abstract; Results p.108","truncated":false},{"metric":"Comparison","text":"no statistically significant difference in AUC0–last and Cmax of silybin A or silybin B between male and female participants could be observed (P > 0.05)","source":"fulltext","location":"Results p.110 (Supplemental Table I)","truncated":false}]},{"id":"pmid-30108644","title":"The Bioavailability and Pharmacokinetics of Silymarin SMEDDS Formulation Study in Healthy Thai Volunteers.","year":"2018","journal":"Evidence-based complementary and alternative medicine : eCAM","pmid":"30108644","pmcid":null,"doi":"10.1155/2018/1507834","url":"https://pubmed.ncbi.nlm.nih.gov/30108644/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/30108644/","doiUrl":"https://doi.org/10.1155/2018/1507834","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6077530/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"single-arm","n":"12","formsStudiedRaw":"Milk thistle (silymarin SMEDDS)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"It showed a fast absorption (tmax < 1 h) and high oral bioavailability (Cmax: 812.43 ng/ml, AUC0-t: 658.80 ng.h/ml).","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"Tmax","text":"tmax (0.54 ± 0.19 versus 1.06 ± 0.48 h) (p<0.05)","source":"fulltext","location":"Results 3.1 (p.4)","truncated":false},{"metric":"Comparison","text":"no difference between male and female volunteers except for tmax (0.54 ± 0.19 versus 1.06 ± 0.48 h) (p<0.05)","source":"fulltext","location":"Results 3.1","truncated":false},{"metric":"Comparison","text":"the Cmax and AUC were approximately 4.9–5.9 and 1.7–2.5 times higher than a conventional capsule","source":"fulltext","location":"Discussion p.5; Table 4","truncated":false}]},{"id":"pmid-28098838","title":"Role of UDP-Glucuronosyltransferase 1A1 in the Metabolism and Pharmacokinetics of Silymarin Flavonolignans in Patients with HCV and NAFLD.","year":"2017","journal":"Molecules (Basel, Switzerland)","pmid":"28098838","pmcid":null,"doi":"10.3390/molecules22010142","url":"https://pubmed.ncbi.nlm.nih.gov/28098838/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/28098838/","doiUrl":"https://doi.org/10.3390/molecules22010142","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6155777/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"other (secondary analysis of Phase 1 randomized dose-escalation trial, SyNCH, NCT00389376, plus in vitro enzyme kinetics)","n":"29 analysed for genotype-PK (56 enrolled; 33 genotyped)","formsStudiedRaw":"Milk thistle (silymarin; silybin A and silybin B)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"our results indicate the UGT1A1*28 allele has no significant effect on the pharmacokinetics of silybin A and silybin B in patients with NAFLD or chronic HCV infection.","source":"fulltext","location":"Conclusions p.13","truncated":false},{"metric":"Comparison","text":"no significant differences were observed in the AUC0–48 h for either SA or SB among UGT1A1 genotypes","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Comparison","text":"7.4 and 4.5 for SA (p < 0.005)","source":"fulltext","location":"Results 2.3; Fig 2","truncated":false},{"metric":"Comparison","text":"68.6 and 43.4 for silybin B (SB) (p = 0.016)","source":"fulltext","location":"Results 2.3; Fig 2","truncated":false},{"metric":"Comparison","text":"did not differ among UGT1A1 *1/*1, *1/*28, and *28/*28 genotypes","source":"fulltext","location":"Results 2.2; Fig 1C,D","truncated":false}]},{"id":"pmid-26595166","title":"The influence of ABCB1 polymorphism C3435T on the pharmacokinetics of silibinin.","year":"2015","journal":"Journal of clinical pharmacy and therapeutics","pmid":"26595166","pmcid":null,"doi":"10.1111/jcpt.12336","url":"https://pubmed.ncbi.nlm.nih.gov/26595166/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/26595166/","doiUrl":"https://doi.org/10.1111/jcpt.12336","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"single-arm","n":"23","formsStudiedRaw":"Silymarin capsule (Legalon); silibinin measured","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"This study shows that the pharmacokinetics of silibinin is significantly influenced by ABCB1 C3435T polymorphism, Dosage adjustment may be necessary for subjects of different genotypes to ensure comparative exposures. A dose-ranging clinical trial should be undertaken to determine whether the observed differences are clinically significant.","source":"fulltext","location":"What is new and conclusion (p. 687)","truncated":false},{"metric":"Comparison","text":"Cmax of subjects with CC and CT genotypes were more than twice higher of that of the subjects with TT genotype (P = 0.0007 and P = 0.0115 respectively)","source":"fulltext","location":"Table 2; Results","truncated":false},{"metric":"Comparison","text":"(with P = 0.0007 and P = 0.0115 respectively)","source":"fulltext","location":"Abstract; Results","truncated":false},{"metric":"Comparison","text":"0.0026","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"AUC0-∞ of CC carriers was particularly higher than that of the TT carriers (P = 0.0216)","source":"fulltext","location":"Table 2; Results","truncated":false},{"metric":"Comparison","text":"AUC0-∞ of CC carriers (347.1 ± 133.8 ng/mL h) was significantly higher than that of TT carriers (228.3 ± 52.9 ng/mL h) (P = 0.0115)","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"0.0648","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"tmax and t1/2 were no different among the ABCB1 genotypes","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"0.65834","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"0.21106","source":"fulltext","location":"Table 2","truncated":false}]},{"id":"pmid-26642669","title":"RATIONALIZED AND COMPLEMENTARY FINDINGS OF SILYMARIN (MILK THISTLE) IN PAKISTANI HEALTHY VOLUNTEERS.","year":"2015","journal":"Acta poloniae pharmaceutica","pmid":"26642669","pmcid":null,"doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/26642669/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/26642669/","doiUrl":null,"pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"parallel (comparative parallel design by gender)","n":"16","formsStudiedRaw":"Silymarin (milk thistle), 200 mg tablets","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"On the bases of observed variations in pharmacokinetics of silymarin in male and female it will be right to say that gender based evidence should be provided if clinical study is reported especially on human being. It is evident that the dose of silymarin must be adjusted prior to administration according to demographic parameters of the patient.","source":"fulltext","location":"Conclusions (p. 613)","truncated":false},{"metric":"Comparison","text":"*sig = significant, **ns = not significant.","source":"fulltext","location":"Table 3","truncated":false}]},{"id":"pmid-24317417","title":"Development and validation of two liquid chromatography-tandem mass spectrometry methods for the determination of silibinin and silibinin hemisuccinate in human plasma.","year":"2014","journal":"Journal of chromatography. B, Analytical technologies in the biomedical and life sciences","pmid":"24317417","pmcid":null,"doi":"10.1016/j.jchromb.2013.11.028","url":"https://pubmed.ncbi.nlm.nih.gov/24317417/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/24317417/","doiUrl":"https://doi.org/10.1016/j.jchromb.2013.11.028","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"randomized crossover (described as randomized, open-label, crossover study)","n":"6","formsStudiedRaw":"Milk thistle (silibinin / silibinin hemisuccinate, IV)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The methods were suitable for pharmacokinetic studies and were successfully applied to human plasma samples from subjects treated intravenously with Legalon SIL at the dose of 20 mg/kg, expressed as silibinin.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"Cmax (µg/mL): 0.4 ± 0.1 (silibinin A); 0.05 ± 0.02 (silibinin B); 55.0 ± 7.9 (silibinin hemisuccinate A); 28.3 ± 3.9 (silibinin hemisuccinate B).","source":"fulltext","location":"Results 3.3 p.7","truncated":false},{"metric":"AUC","text":"AUCt (µg/mL h): 2.1 ± 0.8 (silibinin A); 0.3 ± 0.1 (silibinin B); 210.7 ± 42.5 (silibinin hemisuccinate A); 86.2 ± 14.6 (silibinin hemisuccinate B).","source":"fulltext","location":"Results 3.3 p.7","truncated":false},{"metric":"Comparison","text":"both the Cmax and AUCt values of silibinin A were 6–8-folds higher than the corresponding values of silibinin B","source":"fulltext","location":"Results 3.3 p.8","truncated":false},{"metric":"Comparison","text":"both the Cmax and AUCt values of silibinin hemisuccinate A were 1.5–2.4-folds higher than the corresponding values of silibinin hemisuccinate B","source":"fulltext","location":"Results 3.3 p.8","truncated":false}]},{"id":"pmid-23835761","title":"An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study.","year":"2013","journal":"Drug metabolism and disposition: the biological fate of chemicals","pmid":"23835761","pmcid":null,"doi":"10.1124/dmd.113.052423","url":"https://pubmed.ncbi.nlm.nih.gov/23835761/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/23835761/","doiUrl":"https://doi.org/10.1124/dmd.113.052423","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3876803/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"open-label dose escalation (single doses of 1, 2, 3 capsules on three occasions, then 28-day repeated dosing)","n":"14","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Pharmacokinetic analysis indicated that, in general, silymarin flavonolignans were rapidly absorbed and eliminated with short t1/2 after oral administration of a standardized extract.","source":"fulltext","location":"Discussion p.1683","truncated":false},{"metric":"Comparison","text":"apparent clearance of silybin B, which was significantly greater than silybin A","source":"fulltext","location":"Abstract; Discussion p.1684","truncated":false},{"metric":"Comparison","text":"apparent clearance of isosilybin B was significantly lower than isosilybin A","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"evidence of dose proportionality as assessed by the observed mean Cmax and AUC0-24","source":"fulltext","location":"Results p.1682","truncated":false}]},{"id":"pmid-23072776","title":"Absorption and metabolism of milk thistle flavanolignans in humans.","year":"2012","journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology","pmid":"23072776","pmcid":null,"doi":"10.1016/j.phymed.2012.09.004","url":"https://pubmed.ncbi.nlm.nih.gov/23072776/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/23072776/","doiUrl":"https://doi.org/10.1016/j.phymed.2012.09.004","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"single-arm","n":"15","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"milk thistle flavonolignans are extensively modified after ingestion and recovered in urine as sulpho- and glucuronyl-conjugates, indicating a strong affinity for hepatic phase II enzymes.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Urinary excretion","text":"glucuronides were the major excreted form, with a total excretion equal to 1.37 µmol","source":"fulltext","location":"Results p.43","truncated":false},{"metric":"Urinary excretion","text":"compared to 0.53 and 0.25 µmol of sulphate–glucuronides and diglucuronides","source":"fulltext","location":"Results p.43","truncated":false},{"metric":"Urinary excretion","text":"0.53 and 0.25 µmol of sulphate–glucuronides and diglucuronides, respectively","source":"fulltext","location":"Results p.43","truncated":false},{"metric":"Urinary excretion","text":"The amount of aglycone flavonolignans excreted was 0.02 µmol","source":"fulltext","location":"Results p.43","truncated":false},{"metric":"Urinary excretion","text":"although 2.17 µmol of total flavanolignans were excreted on average","source":"fulltext","location":"Discussion p.44","truncated":false},{"metric":"Absolute bioavailability","text":"The bioavailability of milk thistle flavanolignans was 0.45 ± 0.28% (mean ± SD)","source":"fulltext","location":"Abstract; Results p.44","truncated":false},{"metric":"Tmax","text":"The excretion of monoglucuronides peaked 2 h after consumption","source":"fulltext","location":"Abstract; Results p.44","truncated":false}]},{"id":"pmid-21315924","title":"Stripping voltammetric determination of silymarin in formulations and human blood utilizing bare and modified carbon paste electrodes.","year":"2011","journal":"Talanta","pmid":"21315924","pmcid":null,"doi":"10.1016/j.talanta.2011.01.027","url":"https://pubmed.ncbi.nlm.nih.gov/21315924/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/21315924/","doiUrl":"https://doi.org/10.1016/j.talanta.2011.01.027","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"single-arm","n":"4","formsStudiedRaw":"Milk thistle (silymarin, SMR)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The pharmacokinetic parameters of silymarin in plasma of healthy human volunteers were estimated following the administration of a single oral dose of 120 mg silymarin utilizing the modified carbon paste electrode. The estimated pharmacokinetic parameters were favorably compared with those reported in literature.","source":"fulltext","location":"Abstract","truncated":false}]},{"id":"pmid-21865319","title":"Differences in the disposition of silymarin between patients with nonalcoholic fatty liver disease and chronic hepatitis C.","year":"2011","journal":"Drug metabolism and disposition: the biological fate of chemicals","pmid":"21865319","pmcid":null,"doi":"10.1124/dmd.111.040212","url":"https://pubmed.ncbi.nlm.nih.gov/21865319/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/21865319/","doiUrl":"https://doi.org/10.1124/dmd.111.040212","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3226378/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"RCT (double-blind, placebo-controlled phase 1 dose-escalation; PK reported for silymarin recipients)","n":"40 enrolled (8 per cohort); PK data n=6 per cohort (HCV 560 mg steady-state n=5)","formsStudiedRaw":"Milk thistle (silymarin, Legalon)","formTags":["silymarin"],"food":true,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In summary, the efficacy of silymarin may be more readily observed in NAFLD patients because of their higher flavonolignan plasma concentrations and more extensive enterohepatic cycling compared with those in HCV patients.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"The steady-state pharmacokinetics of silychristin ... were characterized by a Cmax of 67 ng/ml (−2.5 to 174)","source":"fulltext","location":"Results p.2186","truncated":false},{"metric":"Cmax","text":"Silychristin and silydianin were not detected in the plasma of HCV subjects.","source":"fulltext","location":"Fig. 2","truncated":false},{"metric":"Comparison","text":"the adjusted mean AUC0–8 h for silybin B was higher for NAFLD than for HCV (p = 0.004)","source":"fulltext","location":"Results p.2185","truncated":false},{"metric":"Comparison","text":"adjusted mean AUC0–8 h for silybin B conjugates was significantly lower for NAFLD compared with HCV (p = 0.03)","source":"fulltext","location":"Results p.2186","truncated":false},{"metric":"Comparison","text":"silybin A and silybin B AUC0–8 h differed significantly between the 280- and 560-mg dose groups (p ≤ 0.004)","source":"fulltext","location":"Results p.2185","truncated":false},{"metric":"Comparison","text":"AUC0–8 h values for silybin A conjugates and for silybin B conjugates differed significantly between the 280- and 560-mg dose groups (p ≤ 0.004)","source":"fulltext","location":"Results p.2186","truncated":false},{"metric":"Comparison","text":"At the 280-mg dose, no differences were observed in the pharmacokinetics of silybin A or silybin B between HCV and NAFLD subjects","source":"fulltext","location":"Results p.2185","truncated":false},{"metric":"Comparison","text":"Silybin A was the predominant flavonolignan in plasma ... 2.7- to 3.3-fold greater Cmax and a 2- to 4.5-fold greater AUC0–48 h compared with those for silybin B","source":"fulltext","location":"Results p.2184-2185","truncated":false},{"metric":"Comparison","text":"The Cmax and AUC0–8 h for silybin B conjugates were 3- to 4-fold greater than those for silybin A conjugates","source":"fulltext","location":"Results p.2185","truncated":false}]},{"id":"pmid-19841158","title":"Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C.","year":"2010","journal":"Journal of clinical pharmacology","pmid":"19841158","pmcid":null,"doi":"10.1177/0091270009347475","url":"https://pubmed.ncbi.nlm.nih.gov/19841158/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/19841158/","doiUrl":"https://doi.org/10.1177/0091270009347475","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3086763/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"other (double-masked, placebo-controlled, sequential ascending multiple-dose phase I; 3:1 randomization)","n":"32 randomized (4 cohorts of 8); PK n=6 per active cohort (560 mg cohort n=5)","formsStudiedRaw":"Milk thistle (silymarin; silybin A/B, isosilybin A/B, silychristin, silydianin)","formTags":[],"food":true,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Oral doses of silymarin up to 2.1 g per day were safe and well tolerated. The nonlinear pharmacokinetics of silybin A and silybin B suggests low bioavailability associated with customary doses of silymarin may be overcome with doses above 700 mg.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Urinary excretion","text":"Only flavonolignan conjugates were detected in urines and equaled approximately 4.2, 9.6, and 15.8 mg of parent flavonolignan","source":"fulltext","location":"Results text p.445","truncated":false},{"metric":"Urinary excretion","text":"3.1% ± 0.3% (mean ± SD) of the doses administered","source":"fulltext","location":"Results text p.445","truncated":false},{"metric":"Comparison","text":"Sum Parent AUC0-8 h is significantly different for any pair of dose groups","source":"fulltext","location":"Table IV","truncated":false},{"metric":"Comparison","text":"Sum Parent Cmax is only significantly different between the 140- and 700-mg and between the 280- and 700-mg dose groups","source":"fulltext","location":"Table IV","truncated":false},{"metric":"Comparison","text":"differences between dose groups, which ranged from 1.5 to 3.8, did not reach significance (P = .054)","source":"fulltext","location":"Table IV; Results p.440","truncated":false},{"metric":"Comparison","text":"approximately constant dose-normalized AUC0-8 h across all dose groups (P = .42)","source":"fulltext","location":"Table IV; Results p.441","truncated":false},{"metric":"Comparison","text":"silybin A exposures increased approximately 2-, 5-, and 11-fold","source":"fulltext","location":"Results p.439","truncated":false},{"metric":"Comparison","text":"silybin B exposures increased disproportionately by approximately 5-, 8-, and 38-fold","source":"fulltext","location":"Results p.439","truncated":false},{"metric":"Comparison","text":"steady-state total flavonolignan exposures increased approximately 3-, 4-, and 8-fold","source":"fulltext","location":"Results p.440","truncated":false}]},{"id":"pmid-17913795","title":"Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract.","year":"2008","journal":"Drug metabolism and disposition: the biological fate of chemicals","pmid":"17913795","pmcid":null,"doi":"10.1124/dmd.107.017566","url":"https://pubmed.ncbi.nlm.nih.gov/17913795/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/17913795/","doiUrl":"https://doi.org/10.1124/dmd.107.017566","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"single-arm","n":"3","formsStudiedRaw":"Milk thistle extract (silymarin), capsule 1 (Nutraceutical Sciences Institute), labeled 300 mg extract/capsule","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"These data suggest that, after oral administration, silymarin flavonolignans are quickly metabolized to their conjugates, primarily forming glucuronides, and the conjugates are primary components present in human plasma.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"SC Free N.D.","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Cmax","text":"SC Total Cmax 37 ± 7.8","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Tmax","text":"SC Total Tmax 3.7 ± 0.6","source":"fulltext","location":"Table 2","truncated":false},{"metric":"AUC","text":"SC Total AUC0-inf 401 ± 93","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Cmax","text":"SC Conjugated Cmax 37 ± 7.8","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Tmax","text":"SC Conjugated Tmax 3.7 ± 0.6","source":"fulltext","location":"Table 2","truncated":false},{"metric":"AUC","text":"SC Conjugated AUC0-inf 401 ± 93","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"AUC0-inf values of the conjugated and total silymarin flavonolignans were 4- to 30-fold higher than those of their free fractions","source":"fulltext","location":"Abstract","truncated":false}]},{"id":"pmid-18054294","title":"Preparative chromatographic purification of diastereomers of silybin and their quantification in human plasma by liquid chromatography-tandem mass spectrometry.","year":"2008","journal":"Journal of chromatography. B, Analytical technologies in the biomedical and life sciences","pmid":"18054294","pmcid":null,"doi":"10.1016/j.jchromb.2007.10.040","url":"https://pubmed.ncbi.nlm.nih.gov/18054294/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/18054294/","doiUrl":"https://doi.org/10.1016/j.jchromb.2007.10.040","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"single-arm","n":"22","formsStudiedRaw":"Silybin-phosphatidylcholine complex (silybin A and B)","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"This research also outlines a simple, sensitive, selective and reproducible LC-MS-MS method that has been validated for the determination of both silybin A and silybin B in human plasma with a lower limit of quantitation of 2 ng/ml. The LC-MS-MS method described has been successfully applied to pharmacokinetic studies in healthy subjects.","source":"fulltext","location":"Conclusions p.57","truncated":false},{"metric":"Cmax","text":"Cmax silybin A: 2333.7 ± 1037.1 ng/ml","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Cmax","text":"Cmax silybin B: 582.4 ± 350.3 ng/ml","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Tmax","text":"Tmax silybin A: 1.46 ± 0.60 h","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Tmax","text":"Tmax silybin B: 1.36 ± 0.58 h","source":"fulltext","location":"Table 3","truncated":false},{"metric":"AUC","text":"AUC silybin A: 3495.7 ± 1007.5 ng/ml h","source":"fulltext","location":"Table 3","truncated":false},{"metric":"AUC","text":"AUC silybin B: 780.4 ± 301.0 ng/ml h","source":"fulltext","location":"Table 3","truncated":false},{"metric":"AUC","text":"AUC silybin A: 3580.8 ± 1007.2 ng/ml h","source":"fulltext","location":"Table 3","truncated":false}]},{"id":"pmid-18566043","title":"The pharmacokinetics of silymarin is altered in patients with hepatitis C virus and nonalcoholic Fatty liver disease and correlates with plasma caspase-3/7 activity.","year":"2008","journal":"Drug metabolism and disposition: the biological fate of chemicals","pmid":"18566043","pmcid":null,"doi":"10.1124/dmd.107.019604","url":"https://pubmed.ncbi.nlm.nih.gov/18566043/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/18566043/","doiUrl":"https://doi.org/10.1124/dmd.107.019604","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"open-label, nonrandomized, parallel cohorts, single dose","n":"20","formsStudiedRaw":"Milk thistle extract (silymarin), 300 mg capsules standardized to 80% silymarin","formTags":["silymarin"],"food":true,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"These findings suggest that the pharmacokinetics of silymarin is altered in patients with liver disease. Patients with cirrhosis had the highest plasma caspase-3/7 activity and also achieved the highest exposures for the major silymarin flavonolignans.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"12 (2, 67)","source":"fulltext","location":"Table 2","truncated":false},{"metric":"AUC","text":"33 (2, 488)","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Cmax","text":"37 (23, 61)","source":"fulltext","location":"Table 3","truncated":false},{"metric":"AUC","text":"256 (118, 557)","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Cmax","text":"9 (2, 43)","source":"fulltext","location":"Table 2","truncated":false},{"metric":"AUC","text":"23 (2, 302)","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Cmax","text":"106 (63, 177)","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Comparison","text":"The highest exposures were observed for SB, ISA, and SC across all the disease cohorts and were highest in the HCV cirrhosis cohort (p <= 0.02).","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Comparison","text":"NAFLD (p <= 0.03)","source":"fulltext","location":"Results p.1911","truncated":false}]},{"id":"pmid-17077998","title":"A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients.","year":"2007","journal":"Investigational new drugs","pmid":"17077998","pmcid":null,"doi":"10.1007/s10637-006-9019-2","url":"https://pubmed.ncbi.nlm.nih.gov/17077998/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/17077998/","doiUrl":"https://doi.org/10.1007/s10637-006-9019-2","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"phase I dose-escalation, open-label, single-arm (intra-patient escalation allowed)","n":"13","formsStudiedRaw":"Silybin-phytosome (Siliphos), silibinin","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"this study demonstrates the tolerability of high-dose, oral silybin-phytosome in patients with prostate cancer. The most significant toxicity observed was asymptomatic liver abnormalities, most notably unconjugated hyperbilirubinemia, with chronic administration. The recommended phase II oral dose of silybin-phytosome is 13 g daily, in 3 divided doses.","source":"fulltext","location":"Discussion (final paragraph)","truncated":false},{"metric":"Cmax","text":"While some peak plasma levels of silibinin were in excess of 100 µM","source":"fulltext","location":"Discussion","truncated":false},{"metric":"Urinary excretion","text":"The mean silibinin level in the urine was 6.4 µM (range of undetectable to 28.2 µM)","source":"fulltext","location":"Results (Pharmacokinetic studies)","truncated":false},{"metric":"Urinary excretion","text":"the mean silibinin-glucuronide level was 253.4 (range of 1.5–982 µM)","source":"fulltext","location":"Results (Pharmacokinetic studies)","truncated":false},{"metric":"Comparison","text":"Prominent interpatient variability is noted without a clear dose response above the 13 g level.","source":"fulltext","location":"Results / Discussion, Fig. 3","truncated":false}]},{"id":"pmid-16221754","title":"Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans.","year":"2006","journal":"Drug metabolism and disposition: the biological fate of chemicals","pmid":"16221754","pmcid":null,"doi":"10.1124/dmd.105.006312","url":"https://pubmed.ncbi.nlm.nih.gov/16221754/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/16221754/","doiUrl":"https://doi.org/10.1124/dmd.105.006312","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC1865121/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"open-label, randomized sequence, within-subject (each subject received all four interventions), pre/post","n":"16","formsStudiedRaw":"Milk thistle (silymarin 80%, softgel); black cohosh and control drugs also tested","formTags":["silymarin"],"food":true,"timing":false,"relevance":"full-text extraction: off-target analyte (Herb-drug interaction study: measured analyte is digoxin (P-gp substrate), not milk thistle flavanolignans (no silymarin/silibinin plasma levels measured). Digoxin PK extracted as recorded effect of milk thistle on a co-administered drug's absorption.)","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"when compared with the effects of rifampin and clarithromycin, the botanical supplements milk thistle and black cohosh produced no significant changes in the disposition of digoxin, a clinically recognized P-gp substrate with a narrow therapeutic index.","source":"fulltext","location":"Discussion (final paragraph, p.6)","truncated":false},{"metric":"Comparison","text":"Statistically significant increases (p < 0.05) in digoxin AUC(0-24) (35%)","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"approached statistical significance (p = 0.06)","source":"fulltext","location":"Results p.3","truncated":false},{"metric":"Comparison","text":"No significant changes in digoxin pharmacokinetics were observed as a result of milk thistle or black cohosh supplementation","source":"fulltext","location":"Results p.3","truncated":false}]},{"id":"pmid-16432272","title":"Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin.","year":"2006","journal":"Journal of clinical pharmacology","pmid":"16432272","pmcid":null,"doi":"10.1177/0091270005284854","url":"https://pubmed.ncbi.nlm.nih.gov/16432272/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/16432272/","doiUrl":"https://doi.org/10.1177/0091270005284854","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC1865122/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"open-label, randomized sequence, within-subject (each subject received all four interventions), pre/post","n":"19","formsStudiedRaw":"Milk thistle (softgel, 80% silymarin); black cohosh and control drugs also tested","formTags":["silymarin"],"food":true,"timing":false,"relevance":"full-text extraction: off-target analyte (Herb-drug interaction study: measured analyte is midazolam and its metabolite 1-hydroxymidazolam (CYP3A probe), not milk thistle flavanolignans (no silymarin serum concentrations measured). Midazolam PK extracted as the recorded effect of milk thistle on a co-administered drug.)","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"when compared to the effects of rifampin and clarithromycin, the specific brand of milk thistle and black cohosh supplements used in this study produced no significant changes in the disposition of MDZ, a clinically recognized CYP3A substrate. Accordingly, these 2 products appear to pose no clinically significant risk for CYP3A-mediated herb-drug interactions.","source":"fulltext","location":"Discussion (final paragraph, p.211)","truncated":false},{"metric":"Comparison","text":"Statistically significant increases (P < .001) in MDZ AUC0-∞, Cmax, and elimination half-life were observed after 7 days of clarithromycin ingestion","source":"fulltext","location":"Table I","truncated":false},{"metric":"Comparison","text":"A statistically significant reduction in Tmax was also observed following rifampin (P < .05; Table I).","source":"fulltext","location":"Table I","truncated":false},{"metric":"Comparison","text":"no significant changes in MDZ pharmacokinetics were observed as a result of milk thistle or black cohosh supplementation","source":"fulltext","location":"Results p.206; Table I; Table II","truncated":false},{"metric":"Comparison","text":"significant positive correlation between 1-hour HMDZ/MDZ ratios and CL/F/kg (r2 = 0.82, P < .001; Figure 3)","source":"fulltext","location":"Results p.207, Fig. 3","truncated":false}]},{"id":"pmid-17315537","title":"Development of a HPLC-UV assay for silybin-phosphatidylcholine complex (silybinin capsules) and its pharmacokinetic study in healthy male Chinese volunteers.","year":"2006","journal":"European journal of drug metabolism and pharmacokinetics","pmid":"17315537","pmcid":null,"doi":"10.1007/BF03190466","url":"https://pubmed.ncbi.nlm.nih.gov/17315537/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/17315537/","doiUrl":"https://doi.org/10.1007/BF03190466","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"single-arm, open-label single-dose PK study","n":"20","formsStudiedRaw":"Silybin-phosphatidylcholine complex (silybinin capsules)","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"After administration of single oral doses of silybin-phosphatidylcholine complex (equivalent to 280mg silybin) to 20 subjects, Silybin was absorpted rapidly. The times to reach peak plasma concentration (Tmax) ranged from 0.67 to 2.67h, and the mean was 1.4h.","source":"fulltext","location":"Discussion","truncated":false},{"metric":"Cmax","text":"Data were expressed as mean±S.D.","source":"fulltext","location":"Table III","truncated":false},{"metric":"Tmax","text":"the times to reach peak plasma concentration (Tmax) ranged from 0.67 to 2.67h, and the mean was 1.4h","source":"fulltext","location":"Summary / Discussion","truncated":false}]},{"id":"pmid-15666173","title":"Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis.","year":"2005","journal":"European journal of clinical pharmacology","pmid":"15666173","pmcid":null,"doi":"10.1007/s00228-004-0843-z","url":"https://pubmed.ncbi.nlm.nih.gov/15666173/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/15666173/","doiUrl":"https://doi.org/10.1007/s00228-004-0843-z","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"RCT","n":"16","formsStudiedRaw":"Milk thistle (silymarin) as interacting agent; measured drug is indinavir","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: off-target analyte (Randomized controlled drug-interaction study of milk thistle on indinavir pharmacokinetics plus meta-analysis; measured analyte is indinavir, silymarin/silybin not measured. Indinavir data recorded for completeness)","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In our trial, we did not observe an interaction between milk thistle and indinavir.","source":"fulltext","location":"Conclusion p.6","truncated":false},{"metric":"Comparison","text":"All comparisons were non-significant (P>0.31).","source":"fulltext","location":"Results p.4; Table 4","truncated":false},{"metric":"Comparison","text":"Control group mean AUC0-8 decreased ... by 38.5% (90% CI, -55.3% to -15.3%, P=0.01) of baseline at phase III","source":"fulltext","location":"Abstract; Table 2","truncated":false},{"metric":"Comparison","text":"C8 (ng/mL) 208.1 (116.0-373.2) 0.0470","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Comparison","text":"t1/2 (h) 92.2 (83.6-101.6) 0.1623 79.5 (72.1-87.6) 0.0013","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Comparison","text":"non-significant pooled mean difference of 1% in AUC0-8","source":"fulltext","location":"Abstract; Results p.4","truncated":false}]},{"id":"pmid-16278402","title":"Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan.","year":"2005","journal":"Clinical cancer research : an official journal of the American Association for Cancer Research","pmid":"16278402","pmcid":null,"doi":"10.1158/1078-0432.CCR-05-1288","url":"https://pubmed.ncbi.nlm.nih.gov/16278402/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/16278402/","doiUrl":"https://doi.org/10.1158/1078-0432.CCR-05-1288","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"open-label, single-arm, sequential (within-patient: irinotecan alone then with milk thistle), not randomized, no placebo","n":"6","formsStudiedRaw":"Milk thistle seed extract (80% silymarin); silybin measured","formTags":[],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Silybin concentrations after intake of milk thistle are too low to significantly affect the function of CYP3A4 and UGT1A1 in vivo, indicating that milk thistle is unlikely to alter the disposition of anticancer drugs metabolized by these enzymes.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"The maximum plasma concentrations of silybin ranged between 0.0249 and 0.257 Amol/L.","source":"fulltext","location":"Abstract / Results p.5","truncated":false},{"metric":"Comparison","text":"had no significant effect on irinotecan clearance (mean, 31.2 versus 25.4 versus 25.6 L/h; P = 0.16)","source":"fulltext","location":"Abstract / Table 3","truncated":false},{"metric":"Comparison","text":"slightly decreased by milk thistle (2.58% versus 2.23% versus 2.17%; P = 0.047)","source":"fulltext","location":"Abstract / Table 3","truncated":false},{"metric":"Comparison","text":"not statistically significantly associated with AUC ratio of SN-38 to irinotecan (R 2 < 0.092, P > 0.56)","source":"fulltext","location":"Results p.5","truncated":false}]},{"id":"pmid-12885100","title":"Coadministration of milk thistle and indinavir in healthy subjects.","year":"2003","journal":"Pharmacotherapy","pmid":"12885100","pmcid":null,"doi":"10.1592/phco.23.7.866.32723","url":"https://pubmed.ncbi.nlm.nih.gov/12885100/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/12885100/","doiUrl":"https://doi.org/10.1592/phco.23.7.866.32723","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"human","speciesRaw":"human","design":"other (specify)","n":"10","formsStudiedRaw":"Milk thistle (silymarin) as interacting agent; measured drug is indinavir","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: off-target analyte (Drug-interaction study: measured analyte is indinavir plasma PK with and without silymarin; silymarin/silybin concentrations were not measured. Indinavir data are recorded below for completeness)","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Silymarin has no apparent effect on indinavir plasma concentrations.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"AUC","text":"1.38 hr•mg/L [0.79-1.48 hr•mg/L]) was not significant (p=0.64)","source":"fulltext","location":"Results p.3","truncated":false},{"metric":"Cmax","text":"The geometric mean [95% CI] difference in Cmax (1.0 mg/L [0.88-1.4 mg/L]) also was not significant (p=0.30)","source":"fulltext","location":"Results p.3","truncated":false},{"metric":"Relative bioavailability","text":"geometric mean ratio [90% CI] of indinavir AUC 0-8 (0.93 hr•mg/L [0.72-1.2 hr•mg/L])","source":"fulltext","location":"Results p.3","truncated":false},{"metric":"Relative bioavailability","text":"geometric mean ratio [90% CI] of indinavir Cmax (0.89 mg/L [0.72-1.1 mg/L])","source":"fulltext","location":"Results p.3","truncated":false},{"metric":"Comparison","text":"was not significant (p=0.64)","source":"fulltext","location":"Results p.3","truncated":false},{"metric":"Comparison","text":"also was not significant (p=0.30)","source":"fulltext","location":"Results p.3","truncated":false},{"metric":"Comparison","text":"Milk thistle did not significantly influence indinavir trough concentrations.","source":"fulltext","location":"Results p.4","truncated":false}]},{"id":"pmid-37695023","title":"Supplemental impact of silymarin in growing pig diet on the growth performance, total tract digestibility, faecal microflora, faecal noxious gas emission and absorption rate in blood.","year":"2024","journal":"Journal of animal physiology and animal nutrition","pmid":"37695023","pmcid":null,"doi":"10.1111/jpn.13879","url":"https://pubmed.ncbi.nlm.nih.gov/37695023/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/37695023/","doiUrl":"https://doi.org/10.1111/jpn.13879","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"pig","speciesRaw":"pig","design":"parallel","n":"18 (Experiment 2)","formsStudiedRaw":"Milk thistle (silymarin, powdered vs micelle-type)","formTags":["enhanced"],"food":true,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Additionally with the limited number of animal micelle-type silymarin had been found to have a tendency of higher blood absorption rate than powdered silymarin after 1st, 2nd, 4th, 8th, 12th and 24th h of feeding at fattening period.","source":"fulltext","location":"Conclusion","truncated":false},{"metric":"Comparison","text":"micelle-type silymarin showed higher (p < 0.05) absorption rate compared to the powdered type silymarin in 1st, 2nd, 4th, 8th, 12th and 24th h","source":"fulltext","location":"Table 6","truncated":false}]},{"id":"pmid-42264004","title":"Study on the improvement of bioavailability and hepatoprotective effect of silybin-7-eicosanedioate long-acting injection based on prodrug technology.","year":"2026","journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V","pmid":"42264004","pmcid":null,"doi":"10.1016/j.ejpb.2026.115144","url":"https://pubmed.ncbi.nlm.nih.gov/42264004/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/42264004/","doiUrl":"https://doi.org/10.1016/j.ejpb.2026.115144","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups) PK study of an injectable prodrug vs oral capsule","n":"12","formsStudiedRaw":"Milk thistle (silybin/silibinin; SLB-7-ODDA prodrug long-acting injection vs oral silybin capsule)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In conclusion, this formulation significantly prolonged the half-life of SLB, reduced the dosing frequency, and demonstrated excellent sustained-release characteristics and in vivo retention capacity.","source":"fulltext","location":"Section 3.9 / Discussion (p.21)","truncated":false},{"metric":"Relative bioavailability","text":"exhibited a 613.60% higher relative bioavailability compared with the Shuilinjia® Capsules group","source":"fulltext","location":"Table 11; Abstract; Section 3.8","truncated":false},{"metric":"Cmax","text":"lower maximum plasma concentration (Cmax = 1080 ± 500 μg/mL)","source":"fulltext","location":"Results Section 3.8 (p.18)","truncated":false},{"metric":"AUC","text":"AUC(0–t) and AUC(0–∞) values of 326.850 ± 34.180 μg/mL⋅h and 430.550 ± 65.160 μg/mL⋅h","source":"fulltext","location":"Results Section 3.8 (p.18)","truncated":false},{"metric":"Comparison","text":"relative bioavailability of 613.60% compared with marketed SLB capsules","source":"fulltext","location":"Table 11; Abstract","truncated":false},{"metric":"Comparison","text":"significantly prolonged half-life","source":"fulltext","location":"Table 11","truncated":false}]},{"id":"pmid-42497478","title":"Silica-installed redox nanoparticles enable effective oral silymarin therapy for liver fibrosis.","year":"2026","journal":"Colloids and surfaces. B, Biointerfaces","pmid":"42497478","pmcid":null,"doi":"10.1016/j.colsurfb.2026.116000","url":"https://pubmed.ncbi.nlm.nih.gov/42497478/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/42497478/","doiUrl":"https://doi.org/10.1016/j.colsurfb.2026.116000","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (formulation comparison, free vs nanoparticle)","n":null,"formsStudiedRaw":"Milk thistle (silymarin; Sil@siRNP nanoparticle)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"These results demonstrate that siRNP is an effective oral nanoplatform for enhancing the therapeutic efficacy of hydrophobic drugs and highlight the potential of Sil@siRNP as a promising strategy for the treatment of liver fibrosis.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"oral administration of Sil@siRNP significantly increased hepatic accumulation of silymarin compared with free silymarin","source":"fulltext","location":"Results 3.2 / Fig. 2F","truncated":false}]},{"id":"pmid-42956604","title":"Microencapsulated silymarin nanoparticles prepared by atomized instantaneous solidification: Structural characterization, molecular interactions, improved solubility and bioavailability.","year":"2026","journal":"Food chemistry","pmid":"42956604","pmcid":null,"doi":"10.1016/j.foodchem.2026.151735","url":"https://pubmed.ncbi.nlm.nih.gov/42956604/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/42956604/","doiUrl":"https://doi.org/10.1016/j.foodchem.2026.151735","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (4 groups)","n":"24 (4 groups x 6, as stated)","formsStudiedRaw":"Milk thistle (silymarin, SLM)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In vivo studies confirmed enhanced bioavailability and safety of SLM-NMP.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Absolute bioavailability","text":"absolute bioavailability (F) was attained for SLM-NMP, compared to only 0.24% and 27.48% for SLM and SLM-LIP","source":"fulltext","location":"Table 2","truncated":false},{"metric":"AUC","text":"AUC of SLM-NMP silymarin after i.v. administration of 2 mg/kg body weight was 1423.14 ± 568.89 ng/h/ml","source":"fulltext","location":"Table 2 footnote","truncated":false},{"metric":"Comparison","text":"Significant differences (P < 0.05) are indicated with different letters.","source":"fulltext","location":"Table 2","truncated":false}]},{"id":"pmid-39567122","title":"Microwave-assisted, sulfhydryl-modified β-cyclodextrin-silymarin inclusion complex: A diverse approach to improve oral drug bioavailability via enhanced mucoadhesion and permeation.","year":"2025","journal":"Carbohydrate polymers","pmid":"39567122","pmcid":null,"doi":"10.1016/j.carbpol.2024.122880","url":"https://pubmed.ncbi.nlm.nih.gov/39567122/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/39567122/","doiUrl":"https://doi.org/10.1016/j.carbpol.2024.122880","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (4 groups), preclinical formulation comparison","n":null,"formsStudiedRaw":"Milk thistle (silymarin)","formTags":["silymarin"],"food":true,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Moreover, in-vivo studies confirmed a significantly improved oral bioavailability of SMN due to incorporation in sulfhydryl-modified β-CD.","source":"fulltext","location":"Section 4 Conclusion","truncated":false},{"metric":"AUC","text":"AUC of SMN after i.v. administration of 50 mg/kg body weight was 481.4 ± 57.4 μg/mL. h.","source":"fulltext","location":"Table 2 footnote","truncated":false},{"metric":"Cmax","text":"Silymarin exhibited poor drug absorption after oral administration (Cmax 0.25 μg/mL)","source":"fulltext","location":"Results 3.10 p.8","truncated":false},{"metric":"Comparison","text":"A 10-fold enhanced Cmax and 9.06-fold enhanced AUC were observed","source":"fulltext","location":"Table 2; Results 3.10","truncated":false},{"metric":"Comparison","text":"The apparent permeability coefficient (Papp) of SMN was 6.9-fold enhanced on goat intestinal mucosa.","source":"fulltext","location":"Table 1","truncated":false}]},{"id":"pmid-39861153","title":"Silybin Cocrystals with Improved Solubility and Bioavailability.","year":"2025","journal":"Pharmaceuticals (Basel, Switzerland)","pmid":"39861153","pmcid":null,"doi":"10.3390/ph18010090","url":"https://pubmed.ncbi.nlm.nih.gov/39861153/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/39861153/","doiUrl":"https://doi.org/10.3390/ph18010090","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11768837/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (3 groups), randomized, preclinical formulation comparison","n":"18","formsStudiedRaw":"Milk thistle (silybin)","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"At the same dosage, the Silybin cocrystal achieved a 16.4-fold increase in Cmax and a 16.2-fold improvement in AUC0–8h compared to raw Silybin, and also significantly surpassed the bioavailability of the commercial Silybin–phosphatidylcholine complex.","source":"fulltext","location":"Section 4 Conclusions","truncated":false},{"metric":"Comparison","text":"The Cmax and AUC0–8h of the cocrystal are 16.4 and 16.2 times higher than Silybin.","source":"fulltext","location":"Results 2.8; Table 1","truncated":false},{"metric":"Comparison","text":"significantly surpassed the bioavailability of the commercial Silybin–phosphatidylcholine complex","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"Comparison","text":"The Cmax and AUC0–8h of the phosphatidylcholine complex are 8.1 and 6.4 times higher than Silybin.","source":"fulltext","location":"Results 2.8","truncated":false}]},{"id":"pmid-40493802","title":"Discovery of a Novel Silybin Derivative for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis.","year":"2025","journal":"Journal of medicinal chemistry","pmid":"40493802","pmcid":null,"doi":"10.1021/acs.jmedchem.5c00672","url":"https://pubmed.ncbi.nlm.nih.gov/40493802/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/40493802/","doiUrl":"https://doi.org/10.1021/acs.jmedchem.5c00672","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel, preclinical","n":"10","formsStudiedRaw":"Milk thistle (silybin) and its derivative A2","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Furthermore, A2 showed much better bioavailability than silybin and also had a low toxicity profile.","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"Comparison","text":"A2 had over 20 times higher oral bioavailability than silybin.","source":"fulltext","location":"Table 3; Results p.12792","truncated":false}]},{"id":"pmid-40685047","title":"Chitosan-decorated silibinin-hyaluronic acid conjugate for enhancing intestinal absorption and improving liver fibrosis.","year":"2025","journal":"International journal of biological macromolecules","pmid":"40685047","pmcid":null,"doi":"10.1016/j.ijbiomac.2025.146057","url":"https://pubmed.ncbi.nlm.nih.gov/40685047/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/40685047/","doiUrl":"https://doi.org/10.1016/j.ijbiomac.2025.146057","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (parallel-group animal PK, in situ intestinal loop, in vitro release)","n":null,"formsStudiedRaw":"Milk thistle (silibinin/silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Compared with the free SLB group, the CS/HA-SLB NPs group can increase the T1/2 and AUC of SLB, thereby prolonging the circulation time in the body and improving the oral bioavailability of SLB.","source":"fulltext","location":"Conclusion (section 5)","truncated":false},{"metric":"Cmax","text":"Cmax mg/L 4.29 ± 0.25 4.79 ± 0.06 5.39 ± 0.34*","source":"fulltext","location":"Table 1","truncated":false},{"metric":"AUC","text":"AUC0→∞ h•mg/L 10.52 ± 1.99 12.57 ± 1.16 16.71 ± 1.28*","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"P<0.05 versus Free SLB and HA-SLB NPs.","source":"fulltext","location":"Table 1 footnote","truncated":false},{"metric":"Comparison","text":"AUC and MRT of CS/HA-SLB NPs group were remarkable higher than that of HA-SLB NPs group (P < 0.05)","source":"fulltext","location":"Results 3.5","truncated":false},{"metric":"Comparison","text":"CS/HA-SLB NPs group significantly increased the uptake of SLB","source":"fulltext","location":"Results 3.6","truncated":false}]},{"id":"pmid-37774895","title":"Berberine-silybin salt achieves improved anti-nonalcoholic fatty liver disease effect through regulating lipid metabolism.","year":"2024","journal":"Journal of ethnopharmacology","pmid":"37774895","pmcid":null,"doi":"10.1016/j.jep.2023.117238","url":"https://pubmed.ncbi.nlm.nih.gov/37774895/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/37774895/","doiUrl":"https://doi.org/10.1016/j.jep.2023.117238","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":null,"formsStudiedRaw":"Milk thistle (silybin/silibinin) as berberine-silybin salt","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The study demonstrated that compared with physical mixing, salification improved the efficacy of BBR and SIY, as demonstrated in animal experiments.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"For SIY in BSS, the Cmax was increased to 85.7 ng/ml with an AUC of 10.72 ng⋅ml− 1⋅h at 0.5 h.","source":"fulltext","location":"Results 3.4","truncated":false},{"metric":"AUC","text":"with an AUC of 10.72 ng⋅ml− 1⋅h at 0.5 h","source":"fulltext","location":"Results 3.4","truncated":false},{"metric":"Comparison","text":"BSS significantly increased the bioavailability of SIY in both plasma and the liver (2.2- and 4.5-fold, respectively) when compared with BSP","source":"fulltext","location":"Abstract; Results 3.4","truncated":false},{"metric":"Comparison","text":"SIY in BSS exhibited a significantly higher AP-BL Papp and a lower BL-AP Papp than that in BSP","source":"fulltext","location":"Discussion","truncated":false},{"metric":"Comparison","text":"the mean Cmax of SIY in BSS was significantly increased compared to that in BSP and pure SIY groups, both in the plasma and liver","source":"fulltext","location":"Discussion","truncated":false}]},{"id":"pmid-38529622","title":"Rifampin- and Silymarin-Mediated Pharmacokinetic Interactions of Exogenous and Endogenous Substrates in a Transgenic OATP1B Mouse Model.","year":"2024","journal":"Molecular pharmaceutics","pmid":"38529622","pmcid":null,"doi":"10.1021/acs.molpharmaceut.3c01088","url":"https://pubmed.ncbi.nlm.nih.gov/38529622/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/38529622/","doiUrl":"https://doi.org/10.1021/acs.molpharmaceut.3c01088","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11073900/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel groups, drug-interaction PK study","n":null,"formsStudiedRaw":"Milk thistle (silymarin; silybin A/B, silychristin, silydianin, isosilybins)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"we demonstrated the potential utility of the dual humanized OATP1B1/OATP1B3 mice for assessing DDIs and NPDIs.","source":"fulltext","location":"Conclusions (p.2294)","truncated":false},{"metric":"Cmax","text":"yielded silybin A Cmax values of 10.7 µM in the OATP1B mice","source":"fulltext","location":"Discussion p.2293","truncated":false},{"metric":"Comparison","text":"Silymarin had no effect on PIT plasma exposure in FVB mice (AUCR = 0.89)","source":"fulltext","location":"Table 2; Results p.2287","truncated":false},{"metric":"Comparison","text":"a nonsignificant increase in OATP1B mice (AUCR = 1.89)","source":"fulltext","location":"Table 2; Results p.2287","truncated":false},{"metric":"Comparison","text":"Silymarin and rifampin increased PIT Cmax 2.66- and 3.49-fold respectively, compared to vehicle in OATP1B mice.","source":"fulltext","location":"Table 2; Results p.2288","truncated":false},{"metric":"Comparison","text":"silymarin did not significantly affect PRV exposure","source":"fulltext","location":"Table 3; Results p.2288","truncated":false},{"metric":"Comparison","text":"Silymarin and rifampin increased PRV Cmax 1.90- and 2.59-fold respectively, compared to vehicle in OATP1B mice.","source":"fulltext","location":"Table 3; Results p.2288","truncated":false},{"metric":"Comparison","text":"Silymarin had no effect on CP-I AUC0-24h in FVB nor OATP1B mice","source":"fulltext","location":"Tables 4-5; Results p.2288","truncated":false}]},{"id":"pmid-39370820","title":"The Pharmacokinetics and Liver-Targeting Evaluation of Silybin Liposomes Mediated by the NTCP/OCTN2 Dual Receptors.","year":"2024","journal":"Molecular pharmaceutics","pmid":"39370820","pmcid":null,"doi":"10.1021/acs.molpharmaceut.3c01245","url":"https://pubmed.ncbi.nlm.nih.gov/39370820/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/39370820/","doiUrl":"https://doi.org/10.1021/acs.molpharmaceut.3c01245","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (preclinical formulation, IV biodistribution; parallel groups)","n":null,"formsStudiedRaw":"Milk thistle (silybin/silibinin liposomes)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In summary, the developed delivery system increases liver uptake levels and decreases accumulation in off-target tissues by mimicking HBV-targeting properties.","source":"fulltext","location":"Section 4 Conclusions","truncated":false},{"metric":"AUC","text":"The AUC of MyrB/LC Lip@SB in the liver was 66.5, almost twice that of Inj@SB (Figure 12B).","source":"fulltext","location":"Results 3.6 p.4920; Fig. 12B","truncated":false},{"metric":"Comparison","text":"reaching 7.75, which is almost seven times higher than that of Inj@SB","source":"fulltext","location":"Results 3.6; Table 2","truncated":false},{"metric":"Comparison","text":"The uptake of coumarin-6 in dual ligand-modified liposomes by hepatocytes was up to 2.36 μg/mg","source":"fulltext","location":"Abstract; Fig. 8A","truncated":false},{"metric":"Comparison","text":"It can be observed that the lipid bilayer serves as a slow-release mechanism for the drug.","source":"fulltext","location":"Results 3.3.4","truncated":false}]},{"id":"pmid-39418531","title":"Novel Silybin-Conjugated Chitosan Polymeric Micelles for Improving the Oral Absorption of Doxorubicin Based on the Inhibition of P-gp and CYP3A4.","year":"2024","journal":"Biomacromolecules","pmid":"39418531","pmcid":null,"doi":"10.1021/acs.biomac.4c00628","url":"https://pubmed.ncbi.nlm.nih.gov/39418531/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/39418531/","doiUrl":"https://doi.org/10.1021/acs.biomac.4c00628","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (3 groups), preclinical","n":"15","formsStudiedRaw":"Milk thistle (silybin conjugated to chitosan; analyte measured is doxorubicin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: off-target analyte (Rat oral PK of doxorubicin (DOX); silybin is the carrier material (CS-SB micelles) or co-administered, and silybin plasma levels were not measured. DOX PK values recorded for reference.)","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The novel micelle system possessed the capacity to enhance the intestinal absorption of DOX and the potential to reduce DOX cardiotoxicity.","source":"fulltext","location":"Section 4 Conclusions","truncated":false},{"metric":"Relative bioavailability","text":"The micelles showed oral bioavailability of up to 193% versus DOX·HCl.","source":"fulltext","location":"Table 1; Abstract","truncated":false},{"metric":"Comparison","text":"highest oral relative bioavailability (Fr) of 193% and the 4-fold peak concentration (Cmax) compared to that of DOX·HCl","source":"fulltext","location":"Results 3.3 p.7151","truncated":false},{"metric":"Comparison","text":"there was no indication that the oral absorption of DOX was enhanced by the involved SB","source":"fulltext","location":"Results 3.3 p.7151","truncated":false}]},{"id":"pmid-39498271","title":"Study on the preparation of stabilizer-free silymarin nanocrystals and its oral absorption mechanisms.","year":"2024","journal":"International journal of pharmaceutics: X","pmid":"39498271","pmcid":null,"doi":"10.1016/j.ijpx.2024.100292","url":"https://pubmed.ncbi.nlm.nih.gov/39498271/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/39498271/","doiUrl":"https://doi.org/10.1016/j.ijpx.2024.100292","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11533498/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (3 groups), preclinical formulation comparison","n":"15","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The results of pharmacokinetic parameters indicated that SM-NC improved oral bioavailability in rats compared to Crude-SM.","source":"fulltext","location":"Section 4 Conclusions","truncated":false},{"metric":"Relative bioavailability","text":"oral bioavailability of stabilizer-free silymarin nanocrystals was found to be 1.48 times greater than that of the crude drugs","source":"fulltext","location":"Table 1; Abstract","truncated":false},{"metric":"Comparison","text":"*P < 0.05 compared to crude SM","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"the uptake of undissolved SM-NC was significantly higher than that of Crude-SM (P < 0.05)","source":"fulltext","location":"Results 3.4.1","truncated":false},{"metric":"Comparison","text":"the transport of insoluble SM-NC and Crude-SM was significantly lower compared to soluble Crude-SM (P < 0.05)","source":"fulltext","location":"Results 3.4.2","truncated":false}]},{"id":"pmid-36719351","title":"Albumin-Based Silibinin Nanocrystals Targeting Activated Hepatic Stellate Cells for Liver Fibrosis Therapy.","year":"2023","journal":"ACS applied materials & interfaces","pmid":"36719351","pmcid":null,"doi":"10.1021/acsami.2c19269","url":"https://pubmed.ncbi.nlm.nih.gov/36719351/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/36719351/","doiUrl":"https://doi.org/10.1021/acsami.2c19269","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups, PK), preclinical","n":"10 (PK)","formsStudiedRaw":"Silibinin (SLB), free solution vs silibinin-albumin nanocrystals (SLB-HSA NCs)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"SLB-HSA NCs are capable of being a secure and efficient aHSCs-targeted drug delivery system for liver fibrosis therapy.","source":"fulltext","location":"Conclusion p.9","truncated":false},{"metric":"Comparison","text":"SLB-HSA NCs also exhibited more area under curve (AUC0−t), longer mean residence time (MRT0−t), lower clearance rate (CLz), and longer half-life (T1/2z)","source":"fulltext","location":"Table 1","truncated":false}]},{"id":"pmid-36775115","title":"Combinations of grape seed procyanidin extract and milk thistle silymarin extract against lung cancer - The role of MiR-663a and FHIT.","year":"2023","journal":"Life sciences","pmid":"36775115","pmcid":null,"doi":"10.1016/j.lfs.2023.121492","url":"https://pubmed.ncbi.nlm.nih.gov/36775115/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/36775115/","doiUrl":"https://doi.org/10.1016/j.lfs.2023.121492","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":null,"formsStudiedRaw":"Milk thistle (silymarin/silybin; Siliphos phytosome)","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"We also demonstrated the systemic bioavailabilities of LP and siliphos by quantifying plasma GSE, MTE and their respective metabolites.","source":"fulltext","location":"Discussion","truncated":false},{"metric":"Comparison","text":"co-administrations of LP and siliphos did not decrease systemic bioavailabilities of neither agent (Table 2)","source":"fulltext","location":"Results 3.3","truncated":false}]},{"id":"pmid-37457888","title":"Design, Synthesis and Biological Evaluation of Glycosylated Derivatives of Silibinin as Potential Anti-Tumor Agents.","year":"2023","journal":"Drug design, development and therapy","pmid":"37457888","pmcid":null,"doi":"10.2147/DDDT.S404036","url":"https://pubmed.ncbi.nlm.nih.gov/37457888/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/37457888/","doiUrl":"https://doi.org/10.2147/DDDT.S404036","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10349574/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":null,"formsStudiedRaw":"Milk thistle (silibinin) and synthetic glycosylated silibinin derivatives (compounds 14-17)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"All of results supported that the introduction of glycosyl in the 3-OH and 23-OH position of silibinin would be a feasible strategy for developing silibinin derivatives as anti-tumor agents.","source":"fulltext","location":"Conclusion","truncated":false},{"metric":"Comparison","text":"compound 15 showed better metabolic stability with half-life of 128.3 ± 12.0 min in mouse liver microsomes","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Comparison","text":"the synthesized compounds exhibited better solubility in water, ranging from 15.4 mg·L−1 to 33.0 mg·L−1","source":"fulltext","location":"Table 1","truncated":false}]},{"id":"pmid-37506470","title":"Alleviation of acetaminophen-induced liver failure using silibinin nanoliposomes: An in vivo study.","year":"2023","journal":"Biochemical and biophysical research communications","pmid":"37506470","pmcid":null,"doi":"10.1016/j.bbrc.2023.07.045","url":"https://pubmed.ncbi.nlm.nih.gov/37506470/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/37506470/","doiUrl":"https://doi.org/10.1016/j.bbrc.2023.07.045","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"77","formsStudiedRaw":"Milk thistle (silibinin nanoliposomes)","formTags":["phytosome","enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The results of this study support the significant hepatoprotective effect of SLB nanoliposomes against acetaminophen-induced toxicity depending on the route of administration.","source":"fulltext","location":"Abstract","truncated":false}]},{"id":"pmid-37645028","title":"Synthesis, characterization and hepatoprotective effect of silymarin phytosome nanoparticles on ethanol-induced hepatotoxicity in rats.","year":"2023","journal":"BioImpacts : BI","pmid":"37645028","pmcid":null,"doi":"10.34172/bi.2023.24128","url":"https://pubmed.ncbi.nlm.nih.gov/37645028/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/37645028/","doiUrl":"https://doi.org/10.34172/bi.2023.24128","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10460772/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"24","formsStudiedRaw":"Milk thistle (silymarin; silymarin-phosphatidylcholine phytosome)","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Silymarin phytosomal NPs can be used as an efficient treatment for ALD.","source":"fulltext","location":"Abstract","truncated":false}]},{"id":"pmid-38093834","title":"Liposome-Based Silibinin for Mitigating Nonalcoholic Fatty Liver Disease: Dual Effects via Parenteral and Intestinal Routes.","year":"2023","journal":"ACS pharmacology & translational science","pmid":"38093834","pmcid":null,"doi":"10.1021/acsptsci.3c00210","url":"https://pubmed.ncbi.nlm.nih.gov/38093834/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/38093834/","doiUrl":"https://doi.org/10.1021/acsptsci.3c00210","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10714430/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":null,"formsStudiedRaw":"Milk thistle (silibinin, liposomal)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Our study confirmed that Sil-Lip can effectively improve the absorption and bioavailability of Sil, resultantly potentiating its ameliorative effects on NAFLD through modulating intrahepatic insulin resistance-related and NF-κB signaling pathways and extrahepatic gut microbiota.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"the peak plasma concentration (Cmax), area under the curve (AUC), half-life (T1/2), and mean residence time (MRT) of Sil-Lip were 2217.43 ± 159.95 ng/mL, 9778.57 ± 901.39 ng/mL·h, 3.44 ± 0.72 h, and 5.18 ± 0.38 h","source":"fulltext","location":"Results (Sil-Lip Enhanced the Oral Absorption of Sil)","truncated":false},{"metric":"Relative bioavailability","text":"the relative bioavailability of Sil-Lip was 9.45 times higher than that of the free Sil","source":"fulltext","location":"Results (Sil-Lip Enhanced the Oral Absorption of Sil)","truncated":false},{"metric":"Comparison","text":"Sil-Lip can significantly enhance the oral absorption of Sil","source":"fulltext","location":"Results; Fig. 1 caption","truncated":false}]},{"id":"pmid-38139990","title":"Bovine Serum Albumin Nanoparticles Enhanced the Intranasal Bioavailability of Silybin in Rats.","year":"2023","journal":"Pharmaceutics","pmid":"38139990","pmcid":null,"doi":"10.3390/pharmaceutics15122648","url":"https://pubmed.ncbi.nlm.nih.gov/38139990/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/38139990/","doiUrl":"https://doi.org/10.3390/pharmaceutics15122648","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10747608/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (two groups) formulation comparison","n":"14","formsStudiedRaw":"Milk thistle (silybin/silibinin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"the fourfold increase in bioavailability of SLB via intranasal administration of BSA-NP/SLB in a rat model is a significant finding that could revolutionize the administration of SLB and potentially other similar hydrophobic drugs.","source":"fulltext","location":"Conclusions (p.12)","truncated":false},{"metric":"Tmax","text":"Both formulations exhibited a rapid attainment of peak plasma concentration within just 0.5 h","source":"fulltext","location":"Table 3","truncated":false},{"metric":"AUC","text":"the AUC0-24h value of BSA-NP/SLB was four times greater than that of the SLB solution (p < 0.05)","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Relative bioavailability","text":"improved SLB bioavailability by fourfold compared to free SLB","source":"fulltext","location":"Abstract; Results 3.4","truncated":false},{"metric":"Comparison","text":"BSA-NP/SLB outperformed free SLB, yielding a twofold higher Cmax.","source":"fulltext","location":"Results 3.4 p.11","truncated":false},{"metric":"Comparison","text":"The t1/2 of SLB increased threefold in the BSA-NP/SLB group compared to the free SLB group.","source":"fulltext","location":"Results 3.4 p.11","truncated":false}]},{"id":"pmid-35460909","title":"Preclinical validation of silibinin/albumin nanoparticles as an applicable system against acute liver injury.","year":"2022","journal":"Acta biomaterialia","pmid":"35460909","pmcid":null,"doi":"10.1016/j.actbio.2022.04.021","url":"https://pubmed.ncbi.nlm.nih.gov/35460909/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/35460909/","doiUrl":"https://doi.org/10.1016/j.actbio.2022.04.021","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (preclinical formulation/biodistribution/efficacy study)","n":null,"formsStudiedRaw":"Milk thistle (silibinin) - silibinin/bovine serum albumin nanoparticles (SIL/BSA)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"SIL/BSA nanoparticles were successfully prepared to enhance the liver availability of SIL. Both in vivo and in vitro, SIL/BSA nanoparticles exerted ideal hepatoprotective and antioxidant efficacy against acute liver injury, suggesting the promising future in clinical transfer.","source":"fulltext","location":"Abstract (Conclusion)","truncated":false},{"metric":"Comparison","text":"its %ID/g value was 2-fold greater compared with free SIL group","source":"fulltext","location":"Results 3.3","truncated":false}]},{"id":"pmid-35560136","title":"Lung cancer targeting efficiency of Silibinin loaded Poly Caprolactone /Pluronic F68 Inhalable nanoparticles: In vitro and In vivo study.","year":"2022","journal":"PloS one","pmid":"35560136","pmcid":null,"doi":"10.1371/journal.pone.0267257","url":"https://pubmed.ncbi.nlm.nih.gov/35560136/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/35560136/","doiUrl":"https://doi.org/10.1371/journal.pone.0267257","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9106168/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (preclinical parallel-group rat PK, 3 groups)","n":null,"formsStudiedRaw":"Silibinin (milk thistle), free and in PCL/Pluronic F68 nanoparticles","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"SB loaded PCL/ Pluronic F68 nanoparticles were successfully prepared with good entrapment, smaller particle size along uniform spherical shape and good aerosolization behaviour.","source":"fulltext","location":"Conclusion p.26","truncated":false},{"metric":"Relative bioavailability","text":"prepared Inhalable nanoparticles exhibited 4.20 folds more bioavailable than the Nanoparticles by IV Route","source":"fulltext","location":"Results p.25, Pharmacokinetic study","truncated":false},{"metric":"Cmax","text":"Cmax achieved with inhalable nanoparticles was nearly four times higher","source":"fulltext","location":"Results p.24","truncated":false},{"metric":"Comparison","text":"at each time point the plasma concentration of prepared nanoparticles was remarkably higher than those administrated with the SB solution","source":"fulltext","location":"Results p.25","truncated":false}]},{"id":"pmid-35708053","title":"In-depth investigation of the Silymarin effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 and ledipasvir in rat plasma using LC-MS.","year":"2022","journal":"Biomedical chromatography : BMC","pmid":"35708053","pmcid":null,"doi":"10.1002/bmc.5427","url":"https://pubmed.ncbi.nlm.nih.gov/35708053/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/35708053/","doiUrl":"https://doi.org/10.1002/bmc.5427","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (control vs + silymarin), 2 groups","n":"8","formsStudiedRaw":"Silymarin (co-administered with sofosbuvir and ledipasvir)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: off-target analyte (Silymarin was co-administered as a perpetrator; measured PK analytes are sofosbuvir, GS-331007 and ledipasvir (drug-interaction study). Silibinin B was quantified in the method validation but no silymarin/silibinin PK data are reported for the treated rats. Table 4 rows recorded for reference only.)","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"SLY-induced inhibition of SFB and LED metabolism, which could be explained by SLY competitive inhibition of their hepatic uptake associated with a decreased SFB metabolism, appeared in the AUC of GS-331007.","source":"fulltext","location":"Conclusion p.11","truncated":false},{"metric":"Comparison","text":"the AUC of SFB increased significantly in the rat group receiving CMD","source":"fulltext","location":"Table 4; Results p.11","truncated":false},{"metric":"Comparison","text":"CMD administration reduced the AUC of GS-331007","source":"fulltext","location":"Table 4","truncated":false},{"metric":"Comparison","text":"none of the changes in pharmacokinetic parameters reached statistical significance","source":"fulltext","location":"Results p.11","truncated":false}]},{"id":"pmid-35890088","title":"Phytosomes as a Plausible Nano-Delivery System for Enhanced Oral Bioavailability and Improved Hepatoprotective Activity of Silymarin.","year":"2022","journal":"Pharmaceuticals (Basel, Switzerland)","pmid":"35890088","pmcid":null,"doi":"10.3390/ph15070790","url":"https://pubmed.ncbi.nlm.nih.gov/35890088/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/35890088/","doiUrl":"https://doi.org/10.3390/ph15070790","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9318442/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups, PK)","n":null,"formsStudiedRaw":"Silymarin (milk thistle), pure vs phytosome (silymarin-soybean phosphatidylcholine complex)","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"the optimized silymarin phytosomal formulation significantly improved silymarin oral bioavailability as evidenced by a ~6-fold increase in systemic bioavailability compared to pure silymarin.","source":"fulltext","location":"Conclusions p.17","truncated":false},{"metric":"Cmax","text":"Cmax = 1.1 ± 0.12 µg/mL","source":"fulltext","location":"Results 2.10, p.13","truncated":false},{"metric":"Cmax","text":"Cmax = 0.4 ± 0.10 µg/mL","source":"fulltext","location":"Results 2.10, p.13","truncated":false},{"metric":"Relative bioavailability","text":"mean relative bioavailability of the optimized silymarin phytosomal formulation was ~6-fold that of the plain drug","source":"fulltext","location":"Abstract; Results 2.10, p.13","truncated":false},{"metric":"Comparison","text":"optimized silymarin phytosomal formulation showed a significantly higher peak concentration (Cmax = 1.1 ± 0.12 µg/mL) compared to the plain drug","source":"fulltext","location":"Table 5","truncated":false}]},{"id":"pmid-36178580","title":"Enhanced bioavailability and hepatoprotective effect of silymarin by preparing silymarin-loaded solid dispersion formulation using freeze-drying method.","year":"2022","journal":"Archives of pharmacal research","pmid":"36178580","pmcid":null,"doi":"10.1007/s12272-022-01407-0","url":"https://pubmed.ncbi.nlm.nih.gov/36178580/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/36178580/","doiUrl":"https://doi.org/10.1007/s12272-022-01407-0","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (3 groups per experiment), two separate experiments","n":null,"formsStudiedRaw":"Silymarin (milk thistle flavolignans), solid dispersion with Tween 80 and HPC vs silymarin alone, TPGS formulation, and physical mixture","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"the silymarin-SD formulation improved silymarin BA by increasing its solubility, dissolution, and oral absorption via inhibiting silymarin efflux and silymarin glucuronidation in the intestine.","source":"fulltext","location":"Discussion, final paragraph p.16","truncated":false},{"metric":"Relative bioavailability","text":"relative BA of silymarin-SD increased to 215% and 589% compared with silymarin-PM and silymarin alone","source":"fulltext","location":"Table 2; Abstract","truncated":false},{"metric":"Comparison","text":"Both silymarin formulations increased the Cmax and AUC of silymarin compared with those of the silymarin group","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"Cmax and AUC of silymarin-glucuronide were significantly decreased for the silymarin: tween 80:HPC formulation","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"the relative BA increased to 589% compared with the silymarin group","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"Compared to PM, the Tmax of silymarin in the silymarin-SD group was significantly delayed","source":"fulltext","location":"Table 2; Results p.12","truncated":false}]},{"id":"pmid-36557984","title":"Silymarin Protects against Acute Liver Injury Induced by Acetaminophen by Downregulating the Expression and Activity of the CYP2E1 Enzyme.","year":"2022","journal":"Molecules (Basel, Switzerland)","pmid":"36557984","pmcid":null,"doi":"10.3390/molecules27248855","url":"https://pubmed.ncbi.nlm.nih.gov/36557984/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/36557984/","doiUrl":"https://doi.org/10.3390/molecules27248855","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9784215/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (solvent control vs silymarin pretreatment)","n":"12","formsStudiedRaw":"Silymarin (45 mg/kg/day oral, 21 days, as CYP2E1 modulator)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: off-target analyte (Silymarin used as CYP2E1 inhibitor/pretreatment; measured PK analytes are chlorzoxazone (probe) and its metabolite 6-OH-chlorzoxazone in rats (and APAP and its metabolites in mice). Silymarin plasma/liver concentrations are only in Supplementary Table S4 (not in PDF). Table 2/3 recorded for reference only.)","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The results of our study show that silymarin plays an important protective role in the early stage of acetaminophen-induced acute liver injury by reducing the activity and expression of CYP2E1, reducing the generation of toxic metabolites, and alleviating liver injury.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"silymarin pretreatment significantly reduced the conversion of chlorzoxazone to its metabolite 6-OH-CLX and significantly increased the t1/2, area under the curve (AUC) and mean residence time (MRT) of chlorzoxazone","source":"fulltext","location":"Table 2; Results 2.1.2","truncated":false},{"metric":"Comparison","text":"AUC0-t and AUC0-∞ in the SM group were significantly reduced","source":"fulltext","location":"Table 3","truncated":false}]},{"id":"pmid-33246779","title":"Mucoadhesive nanocrystal-in-microspheres with high drug loading capacity for bioavailability enhancement of silybin.","year":"2021","journal":"Colloids and surfaces. B, Biointerfaces","pmid":"33246779","pmcid":null,"doi":"10.1016/j.colsurfb.2020.111461","url":"https://pubmed.ncbi.nlm.nih.gov/33246779/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/33246779/","doiUrl":"https://doi.org/10.1016/j.colsurfb.2020.111461","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (4 formulation groups)","n":null,"formsStudiedRaw":"Silybin (milk thistle), unprocessed vs nanocrystal vs mucoadhesive nanocrystal-in-microspheres","formTags":["enhanced"],"food":true,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The current study demonstrates that the developed delivery vehicle can enhance the bioavailability of SB by increasing its dissolution percentage as well as through extending retention time in the GI tract, and achieve high drug loading capacity.","source":"fulltext","location":"Abstract / Conclusions","truncated":false},{"metric":"AUC","text":"a 3-fold increase of bioavailability (AUC0-24h = 5885.02 ± 623.43 ng h mL) was observed in the coated SBN–C/MS groups","source":"fulltext","location":"Results 3.4 para 2","truncated":false},{"metric":"AUC","text":"compared to the SB groups (AUC0-24h = 2091.91 ± 191.91 ng h mL)","source":"fulltext","location":"Results 3.4 para 2","truncated":false},{"metric":"Cmax","text":"The peak concentrations of SB-NCs, uncoated SB–NC/MS and coated SBNC/MS were 110.75 %, 77.83 % and 64.17 –% higher","source":"fulltext","location":"Results 3.4 para 2","truncated":false},{"metric":"Cmax","text":"110.75 %, 77.83 % and 64.17 –% higher than that of unprocessed SB","source":"fulltext","location":"Results 3.4 para 2","truncated":false},{"metric":"Relative bioavailability","text":"a significant 3-fold increase of drug oral bioavailability compared to unprocessed SB","source":"fulltext","location":"Abstract; Results 3.4","truncated":false},{"metric":"Comparison","text":"a 3-fold increase of bioavailability ... was observed in the coated SBN–C/MS groups compared to the SB groups","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Comparison","text":"coated SB–NC/MS exhibited a pronounced sustained release behavior (Tmax = 6.00 ± 1.27 h)","source":"fulltext","location":"Table 3","truncated":false}]},{"id":"pmid-33257158","title":"Amorphous silibinin nanoparticles loaded into porous starch to enhance remarkably its solubility and bioavailability in vivo.","year":"2021","journal":"Colloids and surfaces. B, Biointerfaces","pmid":"33257158","pmcid":null,"doi":"10.1016/j.colsurfb.2020.111474","url":"https://pubmed.ncbi.nlm.nih.gov/33257158/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/33257158/","doiUrl":"https://doi.org/10.1016/j.colsurfb.2020.111474","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (3 formulation groups, randomised)","n":"18","formsStudiedRaw":"Silibinin (milk thistle), amorphous nanoparticles loaded into porous starch","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"the SNPS might prove to be a preferred alternative to free SLB a formulation for SLB delivery in clinical treatment.","source":"fulltext","location":"Conclusion","truncated":false},{"metric":"Cmax","text":"the Cmax and the AUC(0–t) values of the SNPS ... were 3.36 and 4.28-fold","source":"fulltext","location":"Results 3.5","truncated":false},{"metric":"AUC","text":"were 3.36 and 4.28-fold","source":"fulltext","location":"Results 3.5; Conclusion","truncated":false},{"metric":"Cmax","text":"SN ... were 2.31 and 2.01-fold of the free SLB","source":"fulltext","location":"Results 3.5","truncated":false},{"metric":"Comparison","text":"the SNPS showed a significantly higher plasma concentration of SLB compared with the free SLB and the SN at each time point up to 24 h","source":"fulltext","location":"Results 3.5","truncated":false},{"metric":"Comparison","text":"T1/2 of the SNPS was 2.29 ± 0.25 h, which was significantly prolonged compared to those of the free SLB and the SN","source":"fulltext","location":"Results 3.5","truncated":false}]},{"id":"pmid-33587330","title":"Hepatic organic anion transporting polypeptides mediate disposition of milk thistle flavonolignans and pharmacokinetic silymarin-drug interactions.","year":"2021","journal":"Phytotherapy research : PTR","pmid":"33587330","pmcid":null,"doi":"10.1002/ptr.7049","url":"https://pubmed.ncbi.nlm.nih.gov/33587330/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/33587330/","doiUrl":"https://doi.org/10.1002/ptr.7049","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8217340/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (control vs NASH, vehicle vs silymarin); plus in vitro transporter experiments","n":"26","formsStudiedRaw":"Milk thistle silymarin (flavonolignans: silybin A/B, isosilybin A/B, silychristin, silydianin, taxifolin) given orally","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"OATPs/Oatps transport flavonolignans and are important mediators of pharmacokinetic silymarin-drug interactions. Consuming silymarin doses at or above 700 mg may precipitate pharmacokinetic interactions with OATP drug substrates and place patients at risk for adverse drug reactions.","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"AUC","text":"The combination of silymarin and NASH increased pitavastatin AUC0-27h 5.1-fold compared to the control vehicle group","source":"fulltext","location":"Results 3.2","truncated":false},{"metric":"AUC","text":"NASH alone increased pitavastatin AUC0-27h 2.9-fold (NASH vehicle compared to control vehicle)","source":"fulltext","location":"Results 3.2","truncated":false},{"metric":"AUC","text":"Silymarin increased pitavastatin AUC0-27h 1.8-fold in both the control silymarin and NASH silymarin groups","source":"fulltext","location":"Results 3.2","truncated":false},{"metric":"Cmax","text":"NASH increased pitavastatin Cmax by 3.9-fold in the absence of silymarin","source":"fulltext","location":"Results 3.2","truncated":false},{"metric":"Cmax","text":"and 2.8-fold in the presence of silymarin","source":"fulltext","location":"Results 3.2","truncated":false},{"metric":"Comparison","text":"p-Values ≤.05 versus control silymarin group.","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"no asterisk printed for t1/2 or tmax","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"additive pharmacokinetic effect of silymarin and NASH on pitavastatin systemic exposure","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"MCD diet-induced NASH decreased the expression of Oatp1b2 and Oatp1a4","source":"fulltext","location":"Fig. 3c","truncated":false}]},{"id":"pmid-33616078","title":"Improving silymarin oral bioavailability using silica-installed redox nanoparticle to suppress inflammatory bowel disease.","year":"2021","journal":"Journal of controlled release : official journal of the Controlled Release Society","pmid":"33616078","pmcid":null,"doi":"10.1016/j.jconrel.2020.10.042","url":"https://pubmed.ncbi.nlm.nih.gov/33616078/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/33616078/","doiUrl":"https://doi.org/10.1016/j.jconrel.2020.10.042","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (free silymarin vs SM@siRNP)","n":null,"formsStudiedRaw":"Silymarin (milk thistle) free vs encapsulated in silica-containing redox nanoparticles (SM@siRNP)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The siRNP efficiently encapsulated silymarin to improve the solubility and bioavailability of silymarin.","source":"fulltext","location":"Conclusion","truncated":false},{"metric":"Tmax","text":"absorption of silymarin was detected in the plasma within 0.5 to 2 h after oral administration of SM@siRNP","source":"fulltext","location":"Results 3 (p. 520)","truncated":false},{"metric":"Comparison","text":"AUC ... hundreds of times higher than the AUC of silymarin","source":"fulltext","location":"Results 3; Fig. 4B","truncated":false},{"metric":"Comparison","text":"significantly longer retention of silymarin in the colonic mucosa of mice treated with SM@siRNP","source":"fulltext","location":"Results 3; Fig. 4C,D","truncated":false}]},{"id":"pmid-33925040","title":"Enhanced Bioavailability and Efficacy of Silymarin Solid Dispersion in Rats with Acetaminophen-Induced Hepatotoxicity.","year":"2021","journal":"Pharmaceutics","pmid":"33925040","pmcid":null,"doi":"10.3390/pharmaceutics13050628","url":"https://pubmed.ncbi.nlm.nih.gov/33925040/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/33925040/","doiUrl":"https://doi.org/10.3390/pharmaceutics13050628","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8146637/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (silymarin vs silymarin-SD; single and repeated dose)","n":null,"formsStudiedRaw":"Silymarin (milk thistle), measured as silybin; silymarin-TPGS solid dispersion (silymarin-SD)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"the solid dispersion formulation of silymarin-TPGS may be used to increase solubility and intestinal permeability; therefore, multiple silymarin-SD treatment (at a dose of 20 mg/kg as silybin) exhibited higher plasma concentrations and better hepatoprotective properties than the treatment of silymarin alone in APAP-induced hepatotoxic rats.","source":"fulltext","location":"Discussion (final paragraph)","truncated":false},{"metric":"Cmax","text":"the maximum plasma concentration (Cmax) and the area under the plasma concentration curve (AUC) ... were 4.0- and 1.6-fold, respectively, greater","source":"fulltext","location":"Results 3.4","truncated":false},{"metric":"AUC","text":"were 4.0- and 1.6-fold, respectively, greater than those for silymarin only","source":"fulltext","location":"Results 3.4; Discussion","truncated":false},{"metric":"AUC","text":"the fold increase in the silybin AUC was greater (3.7-fold) in the repeated administration of the silymarin-SD group than silymarin itself (1.6-fold)","source":"fulltext","location":"Results 3.4; Discussion","truncated":false},{"metric":"AUC","text":"plasma AUC was increased 2.1-fold when compared to the single administration of silymarin-SD","source":"fulltext","location":"Discussion","truncated":false},{"metric":"Comparison","text":"* p < 0.05, compared with silymarin itself","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"Tmax and elimination half-life was not different between the silymarin and silymarin-SD groups","source":"fulltext","location":"Results 3.4; Table 1","truncated":false},{"metric":"Comparison","text":"+ p < 0.05, compared with a single administration","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"the liver to plasma AUC ratio of silybin was significantly higher in the silymarin-SD than the silymarin group","source":"fulltext","location":"Fig. 6B","truncated":false}]},{"id":"pmid-31706011","title":"Combinational applicaton of silybin and tangeretin attenuates the progression of non-alcoholic steatohepatitis (NASH) in mice via modulating lipid metabolism.","year":"2020","journal":"Pharmacological research","pmid":"31706011","pmcid":null,"doi":"10.1016/j.phrs.2019.104519","url":"https://pubmed.ncbi.nlm.nih.gov/31706011/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/31706011/","doiUrl":"https://doi.org/10.1016/j.phrs.2019.104519","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (8 groups) animal efficacy study","n":null,"formsStudiedRaw":"Milk thistle (silybin, SB) with tangeretin (TG) as bioavailability enhancer","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In sum, we demonstrated that TG could enhance the therapeutic effect of SB against NASH possibly through regulating the oxidative stress, inflammatory responses, and lipid metabolism as well as enhancing bioavailability.","source":"fulltext","location":"Conclusion (p.8)","truncated":false},{"metric":"Comparison","text":"elevated about 2 fold with co-administration of TG (150 mg/kg)","source":"fulltext","location":"Results 3.3; Fig. 4 legend","truncated":false}]},{"id":"pmid-31923602","title":"Phytosome-nanosuspensions for silybin-phospholipid complex with increased bioavailability and hepatoprotection efficacy.","year":"2020","journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences","pmid":"31923602","pmcid":null,"doi":"10.1016/j.ejps.2020.105212","url":"https://pubmed.ncbi.nlm.nih.gov/31923602/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/31923602/","doiUrl":"https://doi.org/10.1016/j.ejps.2020.105212","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (three groups, randomly divided)","n":null,"formsStudiedRaw":"Milk thistle (silybin) as silybin-phospholipid complex nanosuspension","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Overall, the interesting finding of this study suggested that SPCs-NPs could be applied as a promising formulation for a higher drug bioavailability and better hepatoprotection efficacy.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"AUC","text":"whose AUC0-∞ was only 75.44 ± 8.19 ng/ml × h","source":"fulltext","location":"Results 3.9 p.9","truncated":false},{"metric":"AUC","text":"The AUC0-∞ of SPCs-NPs group was (9407.03 ± 87.45) ng/ml × h","source":"fulltext","location":"Results 3.9 p.9","truncated":false},{"metric":"Comparison","text":"*** p < 0.001 compared with groups of SPCs-NPs and SPCs physical mixture.","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"almost 1.60 times greater than that of SPCs physical mixture","source":"fulltext","location":"Results 3.9","truncated":false}]},{"id":"pmid-32337654","title":"Evaluation of Mogroside V as a Promising Carrier in Drug Delivery: Improving the Bioavailability and Liver Distribution of Silybin.","year":"2020","journal":"AAPS PharmSciTech","pmid":"32337654","pmcid":null,"doi":"10.1208/s12249-020-01645-9","url":"https://pubmed.ncbi.nlm.nih.gov/32337654/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/32337654/","doiUrl":"https://doi.org/10.1208/s12249-020-01645-9","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (two groups) animal studies","n":"10 rats; 18 mice","formsStudiedRaw":"Milk thistle (silybin/silibinin, SLY)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Thus, MOG-V may have the applicability to serve as an ideal excipient for solubilization or as a novel liver targeting carrier for the delivery of SLY.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"**p < 0.01, vs. SLY","source":"fulltext","location":"Table II","truncated":false},{"metric":"Comparison","text":"*p < 0.05, **p < 0.01, vs. SLY","source":"fulltext","location":"Table II","truncated":false}]},{"id":"pmid-32473632","title":"Functional oral nanoparticles for delivering silibinin and cryptotanshinone against breast cancer lung metastasis.","year":"2020","journal":"Journal of nanobiotechnology","pmid":"32473632","pmcid":null,"doi":"10.1186/s12951-020-00638-x","url":"https://pubmed.ncbi.nlm.nih.gov/32473632/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/32473632/","doiUrl":"https://doi.org/10.1186/s12951-020-00638-x","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7260741/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (four groups, randomly assigned)","n":"20 (4 groups of 5)","formsStudiedRaw":"Milk thistle (silibinin/silybin, SLB) co-loaded with cryptotanshinone (CT)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Silibinin- and cryptotanshinone-co-loaded pW-LPNs efficiently penetrate intestinal barriers, thereby enhancing the oral bioavailability of the drug loads.","source":"fulltext","location":"Abstract (Conclusions)","truncated":false},{"metric":"AUC","text":"The area under the curve (AUC) of the S/C-pW-LPNs for SLB was 9,796.75 ± 846.76 μg/L∙h.","source":"fulltext","location":"Results, Pharmacokinetics studies, p.8","truncated":false},{"metric":"Relative bioavailability","text":"The relative bioavailabilities of SLB and CT in the S/W-pW-LPNs were 15.5 × and 11.4 × higher than those in the suspensions","source":"fulltext","location":"Results, Pharmacokinetics studies, p.8","truncated":false},{"metric":"Comparison","text":"This value was 15.9 × , 1.5 × , and 1.13 × higher","source":"fulltext","location":"Results p.8","truncated":false}]},{"id":"pmid-30643408","title":"Co-delivery doxorubicin and silybin for anti-hepatoma via enhanced oral hepatic-targeted efficiency.","year":"2019","journal":"International journal of nanomedicine","pmid":"30643408","pmcid":null,"doi":"10.2147/IJN.S187888","url":"https://pubmed.ncbi.nlm.nih.gov/30643408/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/30643408/","doiUrl":"https://doi.org/10.2147/IJN.S187888","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6314320/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":null,"formsStudiedRaw":"Milk thistle (silybin) co-loaded with doxorubicin in cholic acid-modified liposomes (CA-LP-DOX/SLB)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Concurrent administration of DOX and SLB via CA-LP provided a viable strategy to mitigate acute DOX-induced cardiotoxicity.","source":"fulltext","location":"Abstract","truncated":false}]},{"id":"pmid-30668388","title":"Piperine enhances the bioavailability of silybin via inhibition of efflux transporters BCRP and MRP2.","year":"2019","journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology","pmid":"30668388","pmcid":null,"doi":"10.1016/j.phymed.2018.09.217","url":"https://pubmed.ncbi.nlm.nih.gov/30668388/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/30668388/","doiUrl":"https://doi.org/10.1016/j.phymed.2018.09.217","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"16","formsStudiedRaw":"Milk thistle (silybin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"modulating these transporters by bioenhancer such as piperine could enhance the in vivo absorption of silybin, leading to more effective treatments.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"piperine as a bioenhancer increased the bioavailability of silybin (146%– 181%)","source":"fulltext","location":"Table 1; Results pp.102-103","truncated":false},{"metric":"Comparison","text":"the Tmax, t1/2, and MRT of silybin were not different between the treatment groups","source":"fulltext","location":"Results p.103","truncated":false}]},{"id":"pmid-30766782","title":"Supersaturated polymeric micelles for oral silybin delivery: the role of the Soluplus-PVPVA complex.","year":"2019","journal":"Acta pharmaceutica Sinica. B","pmid":"30766782","pmcid":null,"doi":"10.1016/j.apsb.2018.09.004","url":"https://pubmed.ncbi.nlm.nih.gov/30766782/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/30766782/","doiUrl":"https://doi.org/10.1016/j.apsb.2018.09.004","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6361729/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (4 groups, randomly divided); plus in vitro Caco-2 transport, solubility and supersaturation experiments","n":null,"formsStudiedRaw":"Milk thistle (silybin/silibinin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In conclusion, the Soluplus–PVPVA complex is a potential SDDS for improving the bioavailability of hydrophobic drugs.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"Values are expressed as the mean±SD (n=6).","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Cmax","text":"the Cmax was found to be 3.0 μg/mL and was reached quickly in circulation","source":"fulltext","location":"Table 2; Results 3.5","truncated":false},{"metric":"AUC","text":"The AUC0-1 values ... SDDS-P, SDDS-S and SDDS-SP were 5.8, 4.2, 9.5 μg h/mL","source":"fulltext","location":"Table 2; Results 3.5","truncated":false},{"metric":"Comparison","text":"significantly higher than that of SLB powder (2.1 μg h/mL, P<0.01)","source":"fulltext","location":"Results 3.5","truncated":false},{"metric":"Comparison","text":"**P<0.01 ... versus SLB group","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"The Papp of SDDS-SP was significantly higher than those of SDDS-P and SDDS-S.","source":"fulltext","location":"Results 3.3; Fig. 2C","truncated":false}]},{"id":"pmid-30904740","title":"Development of a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for simultaneous determination of epigallocatechin-3-gallate, silibinin, and curcumin in plasma and different tissues after oral dosing of Protandim in rats and its application in pharmacokinetic and tissue distribution studies.","year":"2019","journal":"Journal of pharmaceutical and biomedical analysis","pmid":"30904740","pmcid":null,"doi":"10.1016/j.jpba.2019.03.024","url":"https://pubmed.ncbi.nlm.nih.gov/30904740/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/30904740/","doiUrl":"https://doi.org/10.1016/j.jpba.2019.03.024","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (cohort A single dose, cohort B multiple dose; one group of rats per time point)","n":null,"formsStudiedRaw":"Milk thistle (silibinin, as component of Protandim)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"No analyte accumulated significantly after multiple doses at the intervals of 24 h. Epigallocatechin-3-gallate, silibinin, and curcumin were distributed mostly in the small intestine, and hardly in skin and brain, but moderately in the kidney, spleen, liver, lung, and heart.","source":"fulltext","location":"Conclusions (section 4)","truncated":false},{"metric":"Comparison","text":"After multiple doses, no significant difference was observed in other pharmacokinetic parameters of plasma, R was 1.01, indicating no significant cumulative effect.","source":"fulltext","location":"Results 3.3","truncated":false}]},{"id":"pmid-31185663","title":"A Simple HPLC Method for the Quantitative Determination of Silybin in Rat Plasma: Application to a Comparative Pharmacokinetic Study on Commercial Silymarin Products.","year":"2019","journal":"Molecules (Basel, Switzerland)","pmid":"31185663","pmcid":null,"doi":"10.3390/molecules24112180","url":"https://pubmed.ncbi.nlm.nih.gov/31185663/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/31185663/","doiUrl":"https://doi.org/10.3390/molecules24112180","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6600178/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (randomly divided into four groups)","n":null,"formsStudiedRaw":"Milk thistle (silymarin commercial products)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The comparative pharmacokinetic study on commercial silymarin products revealed that product #4 significantly enhanced the relative oral bioavailability of SBN compared to product #1–3.","source":"fulltext","location":"Conclusions (section 4)","truncated":false},{"metric":"Comparison","text":"* Significantly different from the other groups (p < 0.05).","source":"fulltext","location":"Table 4; Results 2.3","truncated":false}]},{"id":"pmid-31207432","title":"Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats.","year":"2019","journal":"Pharmacological reports : PR","pmid":"31207432","pmcid":null,"doi":"10.1016/j.pharep.2019.03.013","url":"https://pubmed.ncbi.nlm.nih.gov/31207432/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/31207432/","doiUrl":"https://doi.org/10.1016/j.pharep.2019.03.013","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (animal formulation comparison; in vitro release, cell assays, hepatoprotection and PK sub-studies)","n":"12 (PK study)","formsStudiedRaw":"Milk thistle (silymarin / silybin)","formTags":["phytosome","enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Conventional and PEGylated liposomes of silymarin were found to be more efficacious as hepatoprotective against alcohol-induced hepatotoxicity by its free radical scavenging and anti-inflammatory effects. Conventional liposomes showed enhanced bioavailability compared to silymarin alone.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"Cmax ... was 100.45 ± 3.45 ng/ml for silymarin, with a tmax of 0.5 h","source":"fulltext","location":"Results, Bioavailability study p.8","truncated":false},{"metric":"Comparison","text":"The Cmax was increased in conventional liposomal formulation administered group to 604.48 ± 14.53 ng/ml without any change in tmax.","source":"fulltext","location":"Results p.8 / Table 4","truncated":false},{"metric":"Comparison","text":"The area under the curve (AUC) of the formulation was more than three times higher than silymarin alone","source":"fulltext","location":"Results p.8; Abstract","truncated":false}]},{"id":"pmid-31420525","title":"A Pharmacokinetic Natural Product-Disease-Drug Interaction: A Double Hit of Silymarin and Nonalcoholic Steatohepatitis on Hepatic Transporters in a Rat Model.","year":"2019","journal":"The Journal of pharmacology and experimental therapeutics","pmid":"31420525","pmcid":null,"doi":"10.1124/jpet.119.260489","url":"https://pubmed.ncbi.nlm.nih.gov/31420525/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/31420525/","doiUrl":"https://doi.org/10.1124/jpet.119.260489","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6800447/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (animal PK; 2x2 diet x silymarin/vehicle, IV pitavastatin probe)","n":"16 rats purchased","formsStudiedRaw":"Milk thistle (silymarin; flavonolignans), IV","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"This double hit of NASH and silymarin on hepatic uptake transporters is another example of a multifactorial pharmacokinetic interaction that may have a greater impact on drug disposition than each hit alone.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"AUC","text":"594 ± 71 vs. 353 ± 32 nmol × min/ml, mean ± S.E.M.","source":"fulltext","location":"Results p.388 (text)","truncated":false},{"metric":"Comparison","text":"*P value ≤0.05 vs. control (unpaired t test).","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"Cl of each flavonolignan decreased by 40%–69% in the NASH group","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"(no asterisk in Table 1)","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"594 ± 71 vs. 353 ± 32 nmol × min/ml, mean ± S.E.M.) (P < 0.001)","source":"fulltext","location":"Results p.388","truncated":false}]},{"id":"pmid-28503949","title":"Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization.","year":"2018","journal":"Artificial cells, nanomedicine, and biotechnology","pmid":"28503949","pmcid":null,"doi":"10.1080/21691401.2017.1324465","url":"https://pubmed.ncbi.nlm.nih.gov/28503949/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/28503949/","doiUrl":"https://doi.org/10.1080/21691401.2017.1324465","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":null,"formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Our results concluded that nanoemulsion may be an efficient carrier for oral delivery of silymarin against human hepatocellular carcinoma without damaging normal cells.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"The Cmax of NE9 was found to be 38.62 ± 2.43 µg/ml. That was higher than silymarin-marketed suspension (10.36 ± 1.06) and standard suspension (5.24 ± 4.31)","source":"fulltext","location":"Table 4; Results p.237","truncated":false},{"metric":"Comparison","text":"17-fold higher than standard suspension (17.82 ± 7.32) (p < .01)","source":"fulltext","location":"Table 4; Results p.238","truncated":false},{"metric":"Comparison","text":"8-fold higher than marketed suspension","source":"fulltext","location":"Table 4","truncated":false},{"metric":"Comparison","text":"shorter Tmax (p < .05) compared with conventional and standard suspensions of silymarin (Abstract)","source":"fulltext","location":"Table 4","truncated":false}]},{"id":"pmid-28952834","title":"Silibinin Effect on Fas/FasL, HMGB1, and CD45 Expressions in a Rat Model Subjected to Liver Ischemia-Reperfusion Injury.","year":"2018","journal":"Journal of investigative surgery : the official journal of the Academy of Surgical Research","pmid":"28952834","pmcid":null,"doi":"10.1080/08941939.2017.1360416","url":"https://pubmed.ncbi.nlm.nih.gov/28952834/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/28952834/","doiUrl":"https://doi.org/10.1080/08941939.2017.1360416","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, rat I/R model with IV silibinin; sparse-sampling PK)","n":"73","formsStudiedRaw":"Milk thistle (silibinin) as lyophilized SLB-HP-β-CD complex, IV","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In conclusion, in the present study, the hepatoprotective and anti-inflammatory effect of the antioxidant agent silibinin was demonstrated through the reduction of the expression of specific biomarkers, Fas/FasL, HMGB-1, CD45, in liver tissue under I/R conditions.","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"Comparison","text":"statistically significant at 15 and 45 min for parent (active) SLB after administration (p = .03 and p = .01, respectively)","source":"fulltext","location":"Results p.496","truncated":false},{"metric":"Comparison","text":"statistically nonsignificant at the rest of the elimination phase (p > .1)","source":"fulltext","location":"Results p.496","truncated":false},{"metric":"Comparison","text":"peak liver SLB levels ... were found significantly higher than in PK group at the same time point (p = .003)","source":"fulltext","location":"Results p.496","truncated":false},{"metric":"Comparison","text":"The higher measured liver SLB levels in the Si rats persisted also at 240 min postadministration, the difference being statistically significant (p = .001)","source":"fulltext","location":"Results p.496-498","truncated":false},{"metric":"Comparison","text":"SLB elimination, as reflected on the calculated kel and t1/2 values, is significantly retarded (p = .03) in Si animals","source":"fulltext","location":"Results p.498","truncated":false}]},{"id":"pmid-28958806","title":"Role of tangeretin as a potential bioavailability enhancer for silybin: Pharmacokinetic and pharmacological studies.","year":"2018","journal":"Pharmacological research","pmid":"28958806","pmcid":null,"doi":"10.1016/j.phrs.2017.09.019","url":"https://pubmed.ncbi.nlm.nih.gov/28958806/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/28958806/","doiUrl":"https://doi.org/10.1016/j.phrs.2017.09.019","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, rat PK with bioenhancer; in vitro transporter studies)","n":"18 (PK study, 3 groups of 6)","formsStudiedRaw":"Milk thistle (silybin), oral","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"pharmacokinetic and pharmacological studies demonstrated that tangeretin is a promising agent as bioenhancer for silybin by modulating the transporter of Mrp2 and Bcrp. The combination of tangeretin and silybin is certainly beneficial to improve bioavailability and therapeutic potential.","source":"fulltext","location":"Discussion, final paragraph (p.164-165)","truncated":false},{"metric":"AUC","text":"1970 ± 329.6 and 1464 ± 168.3ng*h/ml","source":"fulltext","location":"Results 3.7, p.159","truncated":false},{"metric":"AUC","text":"1970 ± 329.6","source":"fulltext","location":"Results 3.7, p.159","truncated":false},{"metric":"Comparison","text":"tangeretin could significantly inhibit the efflux transport of silybin (10 µM) in a dose-dependent manner","source":"fulltext","location":"Results 3.3, p.158; Fig. 3","truncated":false},{"metric":"Comparison","text":"reduced the biliary excretion of silybin (10 µM) about ∼90% (P < 0.001)","source":"fulltext","location":"Results 3.4, p.158","truncated":false}]},{"id":"pmid-29162374","title":"The efficiency and mechanism of N-octyl-O, N-carboxymethyl chitosan-based micelles to enhance the oral absorption of silybin.","year":"2018","journal":"International journal of pharmaceutics","pmid":"29162374","pmcid":null,"doi":"10.1016/j.ijpharm.2017.11.034","url":"https://pubmed.ncbi.nlm.nih.gov/29162374/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/29162374/","doiUrl":"https://doi.org/10.1016/j.ijpharm.2017.11.034","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel groups (5 groups), formulation comparison with i.v. reference","n":"25","formsStudiedRaw":"Milk thistle (silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"OCC micelles were demonstrated to efficiently solubilize SLB into the inner cores. Moreover, OCC-SLB micelles allowed for significant increases in SLB oral bioavailability compared with the SLB suspension","source":"fulltext","location":"Conclusion","truncated":false},{"metric":"AUC","text":"AUC0−24 h of 2.51 ± 0.56 μg h mL−1","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"Only 1.4-fold increase (P > 0.05) in SLB oral bioavailability was achieved","source":"fulltext","location":"Results 3.2, p.235","truncated":false}]},{"id":"pmid-30176941","title":"Chitosan-functionalized lipid-polymer hybrid nanoparticles for oral delivery of silymarin and enhanced lipid-lowering effect in NAFLD.","year":"2018","journal":"Journal of nanobiotechnology","pmid":"30176941","pmcid":null,"doi":"10.1186/s12951-018-0391-9","url":"https://pubmed.ncbi.nlm.nih.gov/30176941/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/30176941/","doiUrl":"https://doi.org/10.1186/s12951-018-0391-9","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6122632/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":null,"formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"CS-LPNs enhanced oral delivery of silymarin and exhibited a desirable lipid-lowering effect in a mouse model.","source":"fulltext","location":"Abstract (Conclusions)","truncated":false},{"metric":"Relative bioavailability","text":"relative bioavailability of CS-LPNs was 1.23-fold and 14.38-fold higher than that of S-LPNs and silymarin suspension","source":"fulltext","location":"Abstract; Results (Pharmacokinetic study)","truncated":false},{"metric":"Relative bioavailability","text":"the bioavailability of CS-LPNs was only 1.23-fold higher than that of the chitosan-free LPNs","source":"fulltext","location":"Results (Pharmacokinetic study); Discussion","truncated":false},{"metric":"Comparison","text":"bioavailability of CS-LPNs was only 1.23-fold higher than that of the chitosan-free LPNs","source":"fulltext","location":"Results; Discussion","truncated":false}]},{"id":"pmid-30416442","title":"Baicalein Enhances the Oral Bioavailability and Hepatoprotective Effects of Silybin Through the Inhibition of Efflux Transporters BCRP and MRP2.","year":"2018","journal":"Frontiers in pharmacology","pmid":"30416442","pmcid":null,"doi":"10.3389/fphar.2018.01115","url":"https://pubmed.ncbi.nlm.nih.gov/30416442/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/30416442/","doiUrl":"https://doi.org/10.3389/fphar.2018.01115","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6212553/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"18 (3 groups of 6)","formsStudiedRaw":"Milk thistle (silybin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"efflux transporters play a critical role in the low bioavailability of silybin, while inhibition of breast cancer resistance protein (BCRP) and multi-drug resistance protein 2 (MRP2) by baicalein can significantly increase the absorption and bio-efficacy of silybin","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"increase in Cmax of total silybin A and B by 283% and 243%, respectively","source":"fulltext","location":"Results p.10","truncated":false},{"metric":"Comparison","text":"Oral coadministration of silybin with baicalein resulted in a significant increase in Cmax of total silybin A and B by 283% and 243%","source":"fulltext","location":"Table 1; Results p.10","truncated":false},{"metric":"Comparison","text":"No significant difference in Tmax was found among the groups studied.","source":"fulltext","location":"Results p.10","truncated":false}]},{"id":"pmid-27436270","title":"Highly bioavailable silibinin nanoparticles inhibit HCV infection.","year":"2017","journal":"Gut","pmid":"27436270","pmcid":null,"doi":"10.1136/gutjnl-2016-312019","url":"https://pubmed.ncbi.nlm.nih.gov/27436270/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/27436270/","doiUrl":"https://doi.org/10.1136/gutjnl-2016-312019","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":null,"formsStudiedRaw":"Milk thistle (silibinin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"we have successfully developed SB-NPs exhibiting potent anti-HCV and antioxidant efficacy, with improved solubility and bioavailability.","source":"fulltext","location":"Discussion p.1860","truncated":false},{"metric":"Tmax","text":"SB-NP displayed higher serum levels of free silibinin, which peaked at 2 hours following oral administration","source":"fulltext","location":"Results p.1858 (High bioavailability of SB-NP)","truncated":false},{"metric":"Comparison","text":"SB-NP displayed higher serum levels of free silibinin, which peaked at 2 hours following oral administration, and continuously maintained higher levels for at least 12 hours","source":"fulltext","location":"Results p.1858; Fig 6A","truncated":false},{"metric":"Comparison","text":"SB-NP treatment resulted in substantially more accumulation of free silibinin in the liver and the lung","source":"fulltext","location":"Results p.1858-1859; Fig 6B","truncated":false}]},{"id":"pmid-27575878","title":"A new drug nanocrystal self-stabilized Pickering emulsion for oral delivery of silybin.","year":"2017","journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences","pmid":"27575878","pmcid":null,"doi":"10.1016/j.ejps.2016.08.047","url":"https://pubmed.ncbi.nlm.nih.gov/27575878/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/27575878/","doiUrl":"https://doi.org/10.1016/j.ejps.2016.08.047","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":null,"formsStudiedRaw":"Milk thistle (silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"With a core–shell structure and good physical stability, SN-SSPE could increase the dissolution rate and oral bioavailability of silybin.","source":"fulltext","location":"Conclusion p.426","truncated":false},{"metric":"Comparison","text":"the AUC of SN-SSPE significantly increased by 4.0 times and 1.6 times compared to silybin coarse powder and SN-NCS","source":"fulltext","location":"Table 1; Results 3.5","truncated":false},{"metric":"Comparison","text":"increased by 4.0 times and 1.6 times compared to silybin coarse powder and SN-NCS (P<0.01)","source":"fulltext","location":"Table 1; Results 3.5","truncated":false},{"metric":"Comparison","text":"the Cmax of the SN-SSPE significantly increased by 3.6 times and 2.5 times, respectively (P<0.01)","source":"fulltext","location":"Table 1; Results 3.5","truncated":false}]},{"id":"pmid-28778838","title":"In vivo fate of lipid-silybin conjugate nanoparticles: Implications on enhanced oral bioavailability.","year":"2017","journal":"Nanomedicine : nanotechnology, biology, and medicine","pmid":"28778838","pmcid":null,"doi":"10.1016/j.nano.2017.07.014","url":"https://pubmed.ncbi.nlm.nih.gov/28778838/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/28778838/","doiUrl":"https://doi.org/10.1016/j.nano.2017.07.014","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, rat oral PK vs reference formulation; plus in vitro Caco-2 models, lymph cannulation, imaging)","n":null,"formsStudiedRaw":"Milk thistle (silybin/silibinin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The oral bioavailability of SB is enhanced by 5-7-fold in comparison with a fast-release formulation. No integral LDCs are detected in plasma confirms the readily degradable nature of LDCs.","source":"fulltext","location":"Abstract","truncated":false}]},{"id":"pmid-29026299","title":"Glycogen-gold nanohybrid escalates the potency of silymarin.","year":"2017","journal":"International journal of nanomedicine","pmid":"29026299","pmcid":null,"doi":"10.2147/IJN.S142497","url":"https://pubmed.ncbi.nlm.nih.gov/29026299/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/29026299/","doiUrl":"https://doi.org/10.2147/IJN.S142497","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5626415/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (4 groups), formulation comparison","n":"24","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Compared to free Sly, GSGNPs exhibited significant hepatoprotection with tenfold increase in the potency due to increased solubility, bioavailability, and profuse gut absorption.","source":"fulltext","location":"Conclusion","truncated":false},{"metric":"Comparison","text":"No significant difference was observed in the Cmax and Tmax between animals treated with free Sly and commercial Sly product","source":"fulltext","location":"Results p.7033-7034","truncated":false}]},{"id":"pmid-26556526","title":"Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration.","year":"2016","journal":"Drug delivery","pmid":"26556526","pmcid":null,"doi":"10.3109/10717544.2015.1108374","url":"https://pubmed.ncbi.nlm.nih.gov/26556526/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/26556526/","doiUrl":"https://doi.org/10.3109/10717544.2015.1108374","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"18 (PK rats)","formsStudiedRaw":"Silybin (milk thistle)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The silybin-loaded micelles could be absorbed in the whole intestine through a passive diffusion mechanism and achieved significantly higher oral bioavailability compared with suspension formulation. ... Therefore, HA-adh-GA20 conjugates show great potential for improving the bioavailability and liver targetability of silybin after oral administration.","source":"fulltext","location":"Conclusion (p. 1828)","truncated":false},{"metric":"Comparison","text":"**p<0.01 versus silybin suspension formulation group","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Comparison","text":"MRT ... was significantly longer than silybin suspension (p<0.05)","source":"fulltext","location":"Table 3; Results p. 1826","truncated":false},{"metric":"Comparison","text":"there was no significant difference between silybin-loaded HA-adh-DOCA10 and HA-adh-GA20 micelles (p>0.05)","source":"fulltext","location":"Results p. 1825-1826","truncated":false},{"metric":"Comparison","text":"showing no significant difference among different drug concentrations (p>0.05)","source":"fulltext","location":"Results p. 1825","truncated":false}]},{"id":"pmid-25735668","title":"Development, optimization and evaluation of long chain nanolipid carrier for hepatic delivery of silymarin through lymphatic transport pathway.","year":"2015","journal":"International journal of pharmaceutics","pmid":"25735668","pmcid":null,"doi":"10.1016/j.ijpharm.2015.02.070","url":"https://pubmed.ncbi.nlm.nih.gov/25735668/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/25735668/","doiUrl":"https://doi.org/10.1016/j.ijpharm.2015.02.070","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (3 groups)","n":"18 (PK)","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"It was evident from the findings that the silymarin loaded NLCs exhibited selective liver uptake through the chylomicron pathway. Therefore, it was concluded that lipid carrier systems utilize the chylomicron pathway for the selective transport of drug entrapped in them to the liver cells.","source":"fulltext","location":"Conclusion (section 8)","truncated":false},{"metric":"Cmax","text":"maximum plasma concentration of 25.525 mg/ml is achieved within Tmax of 4 h","source":"fulltext","location":"Results 7.6.5 p.120","truncated":false},{"metric":"Relative bioavailability","text":"this confirms 2-fold increase in relative bioavailability","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"The peak plasma concentration (Cmax) for silymarin loaded NLC was found to be 25.565 ± 0.969 mg/ml as compared to silymarin suspension whose Cmax was found to be 14.050 ± 0.552 mg/ml","source":"fulltext","location":"Table 8; Abstract","truncated":false},{"metric":"Comparison","text":"When inhibitor solution was given to the rats after dose of NLC loaded silymarin, the concentration of drug in blood decreased","source":"fulltext","location":"Results 7.6.5","truncated":false},{"metric":"Comparison","text":"remarkable liver uptake of silymarin loaded NLC-1 (19.268 ± 1.299 mg/ml) after 2 h of oral administration compared to silymarin suspension (5.40 ± 1.05 mg/ml)","source":"fulltext","location":"Table 9; Results 7.6.6","truncated":false}]},{"id":"pmid-25848259","title":"Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery.","year":"2015","journal":"International journal of nanomedicine","pmid":"25848259","pmcid":null,"doi":"10.2147/IJN.S79522","url":"https://pubmed.ncbi.nlm.nih.gov/25848259/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/25848259/","doiUrl":"https://doi.org/10.2147/IJN.S79522","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4381630/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (formulation x surgery groups)","n":null,"formsStudiedRaw":"Milk thistle (silymarin; analyte silibinin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Our pharmacokinetic results indicate that SNEDDS increase the bioavailability of silibinin above that achieved by suspension and solution formulations of silymarin.","source":"fulltext","location":"Conclusion","truncated":false},{"metric":"Tmax","text":"The peak plasma silibinin level occurred at 2–3 hours post-dosing for PEG 400 and SNEDDS.","source":"fulltext","location":"Results p.2407","truncated":false},{"metric":"Comparison","text":"The AUC of silibinin in RYBG rats receiving SNEDDS (180.15) was higher in comparison with PEG 400 (123.20) and the suspension (72.77). This difference was statistically significant","source":"fulltext","location":"Results p.2407; Fig. 3C","truncated":false},{"metric":"Comparison","text":"SNEDDS showed no difference (P>0.05) from the silymarin solution for values of Cmax and AUC","source":"fulltext","location":"Results p.2407","truncated":false},{"metric":"Comparison","text":"The half-life of the suspension (15.03 hours) was relatively longer (P<0.05) than that for PEG 400 (10.45 hours) and SNEDDS (9.04 hours).","source":"fulltext","location":"Results p.2407","truncated":false},{"metric":"Comparison","text":"the half-life and MRT of silibinin from the suspension and the solution were significantly reduced in RYGB rats when compared with normal rats. Clearance was increased by RYGB.","source":"fulltext","location":"Discussion p.2411","truncated":false}]},{"id":"pmid-26152876","title":"Preparation and performance evaluation of emulsomes as a drug delivery system for silybin.","year":"2015","journal":"Archives of pharmacal research","pmid":"26152876","pmcid":null,"doi":"10.1007/s12272-015-0630-7","url":"https://pubmed.ncbi.nlm.nih.gov/26152876/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/26152876/","doiUrl":"https://doi.org/10.1007/s12272-015-0630-7","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"12","formsStudiedRaw":"Silybin (milk thistle)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Compared to an SIL solution, emulsomes produced sustained release of SIL for up to 48 h after an initial burst release in vitro. ... Following SIL delivery by emulsomes, the area under the curve was 2.2-fold higher and the mean residence time was 2.5-fold higher than the corresponding values recorded using SIL solution. Hence, emulsomes might represent a promising system for improving the bioavailability of lipophilic drugs.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"26.03 ± 2.32* vs 11.75 ± 1.15; * P < 0.05, compared with SIL solution","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"51.51 ± 2.01* vs 20.59 ± 1.02","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"35.98 ± 12.53* vs 16.06 ± 7.81","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"0.16 ± 0.09* vs 0.29 ± 0.15","source":"fulltext","location":"Table 2","truncated":false}]},{"id":"pmid-26222744","title":"Serum and tissue pharmacokinetics of silibinin after per os and i.v. administration to mice as a HP-β-CD lyophilized product.","year":"2015","journal":"International journal of pharmaceutics","pmid":"26222744","pmcid":null,"doi":"10.1016/j.ijpharm.2015.07.060","url":"https://pubmed.ncbi.nlm.nih.gov/26222744/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/26222744/","doiUrl":"https://doi.org/10.1016/j.ijpharm.2015.07.060","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"60","formsStudiedRaw":"Silibinin (milk thistle), SLB-HP-β-CD lyophilized product","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Absolute oral bioavailability of SLB from the lyophilized HP-β-CD-SLB product was found about 50% for total (metabolized and non-metabolized) and 10% for parent (non-metabolized) SLB i.e. 10 times higher that after administration of pure SLB.","source":"fulltext","location":"Conclusions (p. 372)","truncated":false},{"metric":"Absolute bioavailability","text":"Parent SLB (non metabolized) Exhibits 13% absolute oral bioavailability while this value increases to almost 50% for total SLB","source":"fulltext","location":"Table 4","truncated":false},{"metric":"Absolute bioavailability","text":"F = 0.122 (or 12.2%)","source":"fulltext","location":"Results 3.2 / 3.3 (p. 369-370)","truncated":false},{"metric":"Absolute bioavailability","text":"about 50% for total (metabolized and non-metabolized) and 10% for parent (non-metabolized) SLB","source":"fulltext","location":"Conclusion (p. 372)","truncated":false},{"metric":"Relative bioavailability","text":"SLB was found to be almost equally absorbed (F = 0.9) when administered as SLB-HP-β-CD lyophilized product and Siliphos","source":"fulltext","location":"Discussion (p. 371)","truncated":false},{"metric":"Comparison","text":"Absolute oral bioavailability of SLB from the lyophilized SLB-HP-β-CD product was 10 times higher than after administration of pure SLB.","source":"fulltext","location":"Abstract; Results p. 371","truncated":false}]},{"id":"pmid-26543366","title":"Enhanced oral bioavailability of silymarin using liposomes containing a bile salt: preparation by supercritical fluid technology and evaluation in vitro and in vivo.","year":"2015","journal":"International journal of nanomedicine","pmid":"26543366","pmcid":null,"doi":"10.2147/IJN.S92665","url":"https://pubmed.ncbi.nlm.nih.gov/26543366/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/26543366/","doiUrl":"https://doi.org/10.2147/IJN.S92665","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4622520/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (randomly assigned to five groups)","n":null,"formsStudiedRaw":"Silymarin (milk thistle)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In vivo assays showed enhanced oral bioavailability of SM administered in liposomes containing a bile salt when compared with an aqueous SM suspension or commercial SM product. This indicates that SEDS exhibit great potential for the preparation of liposomes with improved solubility and oral bioavailability of SM.","source":"fulltext","location":"Conclusion (p. 6642)","truncated":false},{"metric":"Comparison","text":"*P<0.05, compared to the SM powder (conventional powder formulation).","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Comparison","text":"SM-Lip-SEDS has a higher bioavailability than SM-Lip-RPE and SM-Lip-TFD, possibly because of their smaller particle size and higher EE.","source":"fulltext","location":"Table 3; Results p. 6642","truncated":false},{"metric":"Comparison","text":"the absorption of SM was rapid without any significant differences (Tmax =1.42 hours and 0.92 hours for the SM suspension and commercial product","source":"fulltext","location":"Results p. 6642","truncated":false}]},{"id":"pmid-26770331","title":"Pharmacokinetics of silybin nanoparticles in mice bearing SKOV-3 human ovarian carcinoma xenocraft.","year":"2015","journal":"International journal of clinical and experimental medicine","pmid":"26770331","pmcid":null,"doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/26770331/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/26770331/","doiUrl":null,"pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4694231/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"randomized crossover","n":"12","formsStudiedRaw":"Milk thistle (silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Complex of silybin with nanoparticle prompted sustained release of the drug in vitro and enhanced bioavailability in vivo.","source":"fulltext","location":"Conclusion p.17416","truncated":false},{"metric":"Cmax","text":"silybin suspension was quickly retained through the rat gastrointestinal tract with a Cmax of 134.2 ng/mL at a Tmax of 10 minutes","source":"fulltext","location":"Results p.17415 (Pharmacokinetics section)","truncated":false},{"metric":"Tmax","text":"Cmax of 134.2 ng/mL at a Tmax of 10 minutes","source":"fulltext","location":"Results p.17415","truncated":false},{"metric":"Cmax","text":"nanoparticles accomplished a Cmax of 182.4 ng/mL at a Tmax of 15 minutes","source":"fulltext","location":"Results p.17415","truncated":false},{"metric":"Tmax","text":"Cmax of 182.4 ng/mL at a Tmax of 15 minutes","source":"fulltext","location":"Results p.17415","truncated":false},{"metric":"Relative bioavailability","text":"oral bioavailability of silybin nanoparticle was around 178% as contrasted at that of silybin suspension","source":"fulltext","location":"Results p.17415","truncated":false},{"metric":"Comparison","text":"The difference in Cmax was significantly higher for nanoparticles contrasted with pure silybin suspension.","source":"fulltext","location":"Results p.17414","truncated":false},{"metric":"Comparison","text":"higher maximal silybin concentration in the lungs contrasted with the pure silybin suspension, which was measurably huge","source":"fulltext","location":"Results p.17415","truncated":false},{"metric":"Comparison","text":"oral bioavailability of silybin nanoparticle was around 178%","source":"fulltext","location":"Results p.17415","truncated":false}]},{"id":"pmid-24766208","title":"A novel solid dispersion system for natural product-loaded medicine: silymarin-loaded solid dispersion with enhanced oral bioavailability and hepatoprotective activity.","year":"2014","journal":"Journal of microencapsulation","pmid":"24766208","pmcid":null,"doi":"10.3109/02652048.2014.911375","url":"https://pubmed.ncbi.nlm.nih.gov/24766208/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/24766208/","doiUrl":"https://doi.org/10.3109/02652048.2014.911375","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups)","n":"12","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The SD improved the bioavailability of drug by about 3-fold compared to commercial product in rats. Thus, the silymarin-loaded SD prepared with water, PVP and Tween 80 would be useful to deliver poorly water-soluble silymarin with improved bioavailability.","source":"fulltext","location":"Conclusion","truncated":false},{"metric":"Relative bioavailability","text":"the AUC of drug from SD was about 3-fold higher than that from commercial product","source":"fulltext","location":"Results p.623 / Abstract / Conclusion","truncated":false},{"metric":"Comparison","text":"The SD presented significantly higher AUC and Cmax of drug than did commercial product (p<0.05).","source":"fulltext","location":"Table 3; Results p.623","truncated":false},{"metric":"Comparison","text":"the Tmax, Kel and t1/2 values of drug from the SD did not deviate considerably from those attained by the commercial product","source":"fulltext","location":"Results p.623","truncated":false},{"metric":"Comparison","text":"the initial plasma concentrations of silymarin from the SD, from 0.25 to 6 h, were significantly higher than those of the commercial product (p<0.05)","source":"fulltext","location":"Results p.623; Fig. 7","truncated":false}]},{"id":"pmid-25149982","title":"Silymarin liposomes improves oral bioavailability of silybin besides targeting hepatocytes, and immune cells.","year":"2014","journal":"Pharmacological reports : PR","pmid":"25149982","pmcid":null,"doi":"10.1016/j.pharep.2014.04.007","url":"https://pubmed.ncbi.nlm.nih.gov/25149982/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/25149982/","doiUrl":"https://doi.org/10.1016/j.pharep.2014.04.007","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups)","n":"12","formsStudiedRaw":"Milk thistle (silymarin / silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Incorporating phytosomal form of silymarin in liposomal carrier system showed better in vitro and in vivo hepatoprotection besides showing better anti-inflammatory effects and improvement in histopathological changes as compared to silymarin suspension. These effects were further supported by increase in AUC and Cmax of silybin by silymarin-liposomes compared to silymarin suspension.","source":"fulltext","location":"Conclusion","truncated":false},{"metric":"Relative bioavailability","text":"The liposomal formulation yielded a three and half fold higher bioavailability of silymarin as compared with silymarin suspension.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"Cmax was increased by liposomal formulation to 716.40 ± 42.85 ng/ml without a change in tmax","source":"fulltext","location":"Table 4; Results p.796","truncated":false},{"metric":"Comparison","text":"Decrease in half-life and increase elimination rate constant can be justified by selective clearance of liposome by Kupffer cells.","source":"fulltext","location":"Table 4; Discussion","truncated":false}]},{"id":"pmid-25375210","title":"Silymarin in liposomes and ethosomes: pharmacokinetics and tissue distribution in free-moving rats by high-performance liquid chromatography-tandem mass spectrometry.","year":"2014","journal":"Journal of agricultural and food chemistry","pmid":"25375210","pmcid":null,"doi":"10.1021/jf504139g","url":"https://pubmed.ncbi.nlm.nih.gov/25375210/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/25375210/","doiUrl":"https://doi.org/10.1021/jf504139g","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (3 formulations x IV and oral groups)","n":null,"formsStudiedRaw":"Milk thistle (silymarin; analyte silibinin)","formTags":["phytosome","enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"These results showed that the LSM and ESM encapsulated formulations of silymarin may provide more efficient tissue distribution and increased oral bioavailability, thus improving its therapeutic bioactive properties in the body.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Relative bioavailability","text":"caused their relative bioavailabilities to decrease by 7.45- and 2.2-fold compared to silymarin (free form), respectively","source":"fulltext","location":"Results p.11663","truncated":false},{"metric":"AUC","text":"AUC values of silymarin (free form), LSM, and ESM were found to be 2.04 ± 0.74, 15.17 ± 6.51, 4.48 ± 1.03 min·μg·mL−1","source":"fulltext","location":"Results p.11663","truncated":false},{"metric":"AUC","text":"2.04 ± 0.74, 15.17 ± 6.51, 4.48 ± 1.03 min·μg·mL−1","source":"fulltext","location":"Results p.11663","truncated":false},{"metric":"Comparison","text":"the AUC of LSM was significantly higher than that of silymarin","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"Values for LSM and ESM were both significantly higher (p < 0.05) than for silymarin","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"AUC 4.48 ± 1.03 vs 2.04 ± 0.74 (no footnote b)","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"differences between LSM and ESM were insignificant (p > 0.05)","source":"fulltext","location":"Results p.11663","truncated":false},{"metric":"Comparison","text":"the Tmax values for silymarin (free form), LSM, and ESM were not significantly different (approximately 10 min)","source":"fulltext","location":"Results p.11663","truncated":false}]},{"id":"pmid-24039417","title":"Silymarin-loaded solid nanoparticles provide excellent hepatic protection: physicochemical characterization and in vivo evaluation.","year":"2013","journal":"International journal of nanomedicine","pmid":"24039417","pmcid":null,"doi":"10.2147/IJN.S50683","url":"https://pubmed.ncbi.nlm.nih.gov/24039417/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/24039417/","doiUrl":"https://doi.org/10.2147/IJN.S50683","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3770518/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups)","n":"12 (PK)","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Silymarin-loaded nanoparticles developed using SPG membrane emulsification and spray-drying techniques could be a useful system for delivery of poorly water-soluble silymarin while affording excellent hepatic protection.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Relative bioavailability","text":"the bioavailability of the drug achieved by the nanoparticles was about 1.3-fold higher than that of the commercial product","source":"fulltext","location":"Results p.3341 / Abstract","truncated":false},{"metric":"Comparison","text":"AUC 185.34 ± 25.22* vs 145.18 ± 14.49; *P < 0.05 compared with commercial product","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"Cmax 22.07 ± 2.25* vs 15.36 ± 2.25","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"the time taken to reach peak drug levels for the nanoparticles was significantly shorter","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"the Kel and t1/2 values of the drug did not vary considerably between these two groups","source":"fulltext","location":"Results p.3341","truncated":false},{"metric":"Comparison","text":"initial plasma concentrations of drugs in nanoparticles between 0.25 and 1.5 hours were impressively higher than those in the commercial product (P < 0.05)","source":"fulltext","location":"Results p.3341; Fig. 6","truncated":false}]},{"id":"pmid-21802925","title":"A new approach to enhance oral bioavailability of Silybum Marianum dry extract: association of mechanochemical activation and spray congealing.","year":"2012","journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology","pmid":"21802925","pmcid":null,"doi":"10.1016/j.phymed.2011.06.027","url":"https://pubmed.ncbi.nlm.nih.gov/21802925/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/21802925/","doiUrl":"https://doi.org/10.1016/j.phymed.2011.06.027","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (three groups of five rats)","n":"15","formsStudiedRaw":"Milk thistle (Silybum marianum dry extract, 83% silybin; silybin A and B)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"These microparticles promoted an excellent oral bioavailability in rats of the principal flavolignans of Silybum Marianum dry extract (silybin A and B) thanks to the stable activated solid state of the coground with Ac-Di-Sol and to the efficient dispersion in the amphiphilic Gelucire 50/13.","source":"fulltext","location":"Conclusions (p.167)","truncated":false},{"metric":"Comparison","text":"the relative bioavailability was 2500 for silybine A and 1450 for silybine B with respect of original dry extract","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"(90 and 140 for Silybine A and B, respectively) in comparison to the pure extract in aqueous suspension","source":"fulltext","location":"Table 2","truncated":false}]},{"id":"pmid-20942611","title":"Polyamidoamine dendrimers as potential drug carriers for enhanced aqueous solubility and oral bioavailability of silybin.","year":"2011","journal":"Drug development and industrial pharmacy","pmid":"20942611","pmcid":null,"doi":"10.3109/03639045.2010.518150","url":"https://pubmed.ncbi.nlm.nih.gov/20942611/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/20942611/","doiUrl":"https://doi.org/10.3109/03639045.2010.518150","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"randomized two-period crossover (rats)","n":"12","formsStudiedRaw":"Milk thistle (silybin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Complex of silybin with dendrimers led to sustained release of the drug in vitro and improved bioavailability in vivo.","source":"fulltext","location":"Conclusion (p.426)","truncated":false},{"metric":"Cmax","text":"The administration of silybin-G2 PAMAM mixture achieved a Cmax of 182.4 ng/mL at a Tmax of 15 minutes","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Cmax","text":"silybin suspension was rapidly absorbed through the rat gastrointestinal tract with a Cmax of 134.2 ng/mL at a Tmax of 10 minutes","source":"fulltext","location":"Table 2","truncated":false},{"metric":"AUC","text":"Tmax, Cmax, and AUC0-inf ... 15 minutes, 182.4 ng/mL, 1298.7 (ng·h)/mL","source":"fulltext","location":"Table 2","truncated":false},{"metric":"AUC","text":"10 minutes, 134.2 ng/mL, 654.6 (ng·h)/mL","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Relative bioavailability","text":"the oral bioavailability of silybin-G2 PAMAM mixture was about 178% as compared with that of silybin suspension","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"*P < 0.05 versus suspension of silybin with the silybin-dendrimer complex","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"in vitro release of silybin from the silybin-dendrimer complex was significantly slower compared with pure silybin (P < 0.05)","source":"fulltext","location":"Abstract","truncated":false}]},{"id":"pmid-21111585","title":"Oral bioavailability of silymarin phytocomplex formulated as self-emulsifying pellets.","year":"2011","journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology","pmid":"21111585","pmcid":null,"doi":"10.1016/j.phymed.2010.10.012","url":"https://pubmed.ncbi.nlm.nih.gov/21111585/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/21111585/","doiUrl":"https://doi.org/10.1016/j.phymed.2010.10.012","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (two groups of rats)","n":"8","formsStudiedRaw":"Milk thistle (silymarin; silybin A and B)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"These preliminary technological and pharmacokinetic data demonstrated that extrusion/spheronisation is a viable technology to produce self-emulsifying pellets of good quality and able to improve in vivo oral bioavailability of main components of a phytotherapeutic extract of more than 100 times by enhancing the lymphatic route of absorption.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Fractional absorption","text":"direct absorption of silymarin in plasma lasts for more than 6 h","source":"fulltext","location":"Fig. 5c","truncated":false},{"metric":"Relative bioavailability","text":"Bioavailabilities of silybin A and silybin B were 354 and 131 times respectively higher when administered as pellets compared to dry extract.","source":"fulltext","location":"Results p.509","truncated":false},{"metric":"Comparison","text":"Bioavailabilities of silybin A and silybin B were 354 and 131 times respectively higher when administered as pellets","source":"fulltext","location":"Results p.509","truncated":false},{"metric":"Comparison","text":"silymarin is absorbed through the lymphatic system when administered as pellets, while it was not present in the lymph at the quantifiable levels when administered as dry extract","source":"fulltext","location":"Results p.510","truncated":false}]},{"id":"pmid-21549187","title":"Oil based nanocarrier for improved oral delivery of silymarin: In vitro and in vivo studies.","year":"2011","journal":"International journal of pharmaceutics","pmid":"21549187","pmcid":null,"doi":"10.1016/j.ijpharm.2011.04.041","url":"https://pubmed.ncbi.nlm.nih.gov/21549187/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/21549187/","doiUrl":"https://doi.org/10.1016/j.ijpharm.2011.04.041","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel (three groups of six rats)","n":"18","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The AUC and Cmax of TF14 formulation after oral administration were 4-fold and 6-fold higher than those of drug suspension of silymarin, respectively.","source":"fulltext","location":"Conclusion (p.253)","truncated":false},{"metric":"Comparison","text":"Cmax of TF14 formulation was significantly higher (p < 0.01) than the marketed conventional formulation and bulk drug suspension","source":"fulltext","location":"Results p.252","truncated":false},{"metric":"Comparison","text":"it was insignificant when marketed formulation was compared with the bulk drug suspension (p > 0.05)","source":"fulltext","location":"Results p.252","truncated":false},{"metric":"Comparison","text":"the difference in tmax of TF14 formulation was significant when compared to tmax of marketed formulation and bulk drug suspension (p < 0.01)","source":"fulltext","location":"Results p.252","truncated":false},{"metric":"Comparison","text":"insignificant between bulk drug suspension and marketed formulation (p > 0.05)","source":"fulltext","location":"Results p.252","truncated":false}]},{"id":"pmid-18428992","title":"Solid state mechanochemical simultaneous activation of the constituents of the Silybum marianum phytocomplex with crosslinked polymers.","year":"2009","journal":"Journal of pharmaceutical sciences","pmid":"18428992","pmcid":null,"doi":"10.1002/jps.21417","url":"https://pubmed.ncbi.nlm.nih.gov/18428992/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/18428992/","doiUrl":"https://doi.org/10.1002/jps.21417","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (parallel, three formulations; composite curves)","n":null,"formsStudiedRaw":"Silybum marianum (milk thistle) dry extract: silybin A, silybin B, silychristin","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"It can be concluded that the solid state mechanochemical process is a viable means to increase the in vitro solubilization of various active components and therefore to improve their bioavailability when given by oral route.","source":"fulltext","location":"Conclusions p.226","truncated":false},{"metric":"Tmax","text":"tmax (h) 1.00","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Cmax","text":"Cmax (µg/mL) 0.93","source":"fulltext","location":"Table 3","truncated":false},{"metric":"AUC","text":"AUClast (h × µg/mL) 0.63","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Cmax","text":"Dose-normalized Cmax 0.11","source":"fulltext","location":"Table 3","truncated":false},{"metric":"AUC","text":"Dose-normalized AUClast 0.07","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Relative bioavailability","text":"Frel 1","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Tmax","text":"tmax (h) 0.50","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Comparison","text":"Ac-Di-Sol and PVP-CL led to an oral relative bioavailability with respect to the extract of 88.6 and 34.5, respectively.","source":"fulltext","location":"Table 3; Results p.226","truncated":false}]},{"id":"pmid-19226635","title":"Solid state mechanochemical activation of Silybum marianum dry extract with betacyclodextrins: Characterization and bioavailability of the coground systems.","year":"2009","journal":"Journal of pharmaceutical sciences","pmid":"19226635","pmcid":null,"doi":"10.1002/jps.21704","url":"https://pubmed.ncbi.nlm.nih.gov/19226635/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/19226635/","doiUrl":"https://doi.org/10.1002/jps.21704","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (parallel, two formulations, pilot study, composite plasma curves)","n":null,"formsStudiedRaw":"Milk thistle (Silybum marianum dry extract; silybin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Finally, the in vivo absorption studies in rats revealed a very remarkable improvement of the oral bioavailability of the dry extract with respect to the reference product.","source":"fulltext","location":"Conclusions p.10","truncated":false},{"metric":"Cmax","text":"maximal concentration of 33.2 mg/L compared to 4.1 mg/L obtained with Silirex","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Cmax","text":"reaching a maximal concentration of 33.2 mg/L compared to 4.1 mg/L obtained with Silirex","source":"fulltext","location":"Table 2","truncated":false},{"metric":"AUC","text":"the AUC is in fact 145.4 mgh/L for sodium croscarmellose, 107.8 mgh/L for BCD","source":"fulltext","location":"Table 2; Results p.9","truncated":false},{"metric":"Relative bioavailability","text":"The oral bioavailability of the coground system was 6.6 times higher than that of the commercial product","source":"fulltext","location":"Table 2; Abstract; Results p.9","truncated":false},{"metric":"AUC","text":"the AUC is in fact 145.4 mgh/L for sodium croscarmellose","source":"fulltext","location":"Results p.9 (left column)","truncated":false},{"metric":"AUC","text":"78.4 mgh/L for crospovidone","source":"fulltext","location":"Results p.9 (left column)","truncated":false},{"metric":"Comparison","text":"reaching a maximal concentration of 33.2 mg/L compared to 4.1 mg/L","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"there is no significant difference between every two samples (p > 0.05)","source":"fulltext","location":"Results p.8","truncated":false}]},{"id":"pmid-19470289","title":"Pharmacokinetic interaction between oltipraz and silymarin in rats.","year":"2009","journal":"Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques","pmid":"19470289","pmcid":null,"doi":"10.18433/j38c7w","url":"https://pubmed.ncbi.nlm.nih.gov/19470289/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/19470289/","doiUrl":"https://doi.org/10.18433/j38c7w","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, drug-drug interaction PK study in rats)","n":null,"formsStudiedRaw":"Milk thistle (silymarin / silibinin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"After single intravenous administration of the drugs together, the AUC of unconjugated silibinin was significantly smaller, but that of both conjugated and total silibinin was significantly greater. This could have been due to an increase in the formation of conjugates (glucuronidation and sulfation) of silibinin as induced by oltipraz. After simultaneous oral administration of the drugs, however, the AUCs (or AUC0−12 h) of unconjugated, conjugated, and total silibinin were comparable.","source":"fulltext","location":"Abstract (Conclusions)","truncated":false},{"metric":"Comparison","text":"the AUC of unconjugated silibinin was significantly smaller","source":"fulltext","location":"Table 2; Abstract","truncated":false},{"metric":"Comparison","text":"AUCs of unconjugated, conjugated, and total silibinin were significantly different (32.7% decrease, and 32.1% and 27.2% increase","source":"fulltext","location":"Table 2; Abstract","truncated":false},{"metric":"Comparison","text":"CL and CLNR of the unconjugated silibinin were significantly faster (49.4% and 61.1% increase, respectively)","source":"fulltext","location":"Table 2; Results p.5","truncated":false},{"metric":"Comparison","text":"Vdss of the unconjugated silibinin was significantly larger (131% increase)","source":"fulltext","location":"Table 2; Results p.5","truncated":false},{"metric":"Comparison","text":"did not differ significantly between the two groups of rats","source":"fulltext","location":"Table 4; Results p.7","truncated":false}]},{"id":"pmid-19863195","title":"Self-assembly and characterization of Pluronic P105 micelles for liver-targeted delivery of silybin.","year":"2009","journal":"Journal of drug targeting","pmid":"19863195","pmcid":null,"doi":"10.3109/10611860903062062","url":"https://pubmed.ncbi.nlm.nih.gov/19863195/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/19863195/","doiUrl":"https://doi.org/10.3109/10611860903062062","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, two micelle formulations, IV)","n":null,"formsStudiedRaw":"Milk thistle (silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"LA-P105 has been successfully synthesized and utilized to self-assemble micelles to encapsulate a highly hydrophobic drug, silybin. [...] biodistribution studies confirmed that selective targeting of silybin-loaded LA-P105 micelles into liver occurred in a site-specific manner. In conclusion, LA-P105 is a promising polymer for preparing liver-targeting polymeric micelles.","source":"fulltext","location":"Conclusion p.748","truncated":false},{"metric":"Comparison","text":"The AUC for P105 micelles was markedly higher than that of LA-P105 micelles (P < 0.05)","source":"fulltext","location":"Table 1; Results p.746","truncated":false},{"metric":"Comparison","text":"the MRT of silybin for LA-P105 micelles was significantly prolonged (P < 0.05)","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"TE of liver for LA-P105 micelles was significantly higher than that for P105 micelles (P < 0.001)","source":"fulltext","location":"Fig. 9; Results p.747","truncated":false}]},{"id":"pmid-18048488","title":"Hepatobiliary excretion of silibinin in normal and liver cirrhotic rats.","year":"2008","journal":"Drug metabolism and disposition: the biological fate of chemicals","pmid":"18048488","pmcid":null,"doi":"10.1124/dmd.107.017004","url":"https://pubmed.ncbi.nlm.nih.gov/18048488/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/18048488/","doiUrl":"https://doi.org/10.1124/dmd.107.017004","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, five groups)","n":null,"formsStudiedRaw":"Silibinin (milk thistle), i.v.","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In the DMN-induced liver cirrhotic rats, the AUC of plasma unconjugated silibinin was reduced by 53%; however, total silibinin was increased by 182%. These results together suggest that the phase II conjugative reaction of silibinin was blocked by treatment with DNM.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"AUC","text":"AUC 0.16 ± 0.03","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Cmax","text":"Cmax 28 ± 8","source":"fulltext","location":"Table 1","truncated":false},{"metric":"AUC","text":"AUC 0.2 ± 0.03","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Cmax","text":"Cmax 33 ± 2.9","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Tmax","text":"Tmax 1 ± 0","source":"fulltext","location":"Table 1","truncated":false},{"metric":"AUC","text":"AUC 3.11 ± 0.81","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Cmax","text":"Cmax 37 ± 15","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"unconjugated silibinin concentration and AUC in the plasma were markedly decreased","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"AUC of total silibinin in the plasma ... was significantly increased","source":"fulltext","location":"Table 2","truncated":false}]},{"id":"pmid-17328246","title":"Formulation and biopharmaceutical evaluation of silymarin using SMEDDS.","year":"2007","journal":"Archives of pharmacal research","pmid":"17328246","pmcid":null,"doi":"10.1007/BF02977782","url":"https://pubmed.ncbi.nlm.nih.gov/17328246/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/17328246/","doiUrl":"https://doi.org/10.1007/BF02977782","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (rat PK, test vs reference; design as printed not stated as crossover/parallel)","n":null,"formsStudiedRaw":"Silymarin (milk thistle), silybin measured; SMEDDS vs Legalon reference capsule","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"After oral administration to rats, the SMEDDS containing silymarin had a 360% higher bioavailability compared with the reference capsule.","source":"fulltext","location":"Conclusion p.87","truncated":false},{"metric":"Tmax","text":"Tmax, h 1.10 ± 0.48 (reference capsule)","source":"fulltext","location":"Table II","truncated":false},{"metric":"Tmax","text":"Tmax, h 0.50 ± 0.00 (SMEDDS)","source":"fulltext","location":"Table II","truncated":false},{"metric":"Cmax","text":"Cmax, µg/mL 3.47 ± 0.20","source":"fulltext","location":"Table II","truncated":false},{"metric":"Cmax","text":"Cmax, µg/mL 24.79 ± 4.69","source":"fulltext","location":"Table II","truncated":false},{"metric":"AUC","text":"AUC, µg·h/mL 22.75 ± 3.19","source":"fulltext","location":"Table II","truncated":false},{"metric":"AUC","text":"AUC, µg·h/mL 81.88 ± 12.86","source":"fulltext","location":"Table II","truncated":false},{"metric":"Relative bioavailability","text":"The calculated relative bioavailability of the SMEDDS compared to the reference capsule was 360%.","source":"fulltext","location":"Results p.87 (Pharmacokinetic study)","truncated":false},{"metric":"Comparison","text":"SMEDDS resulted in significantly higher improvement of drug absorption than the reference capsule.","source":"fulltext","location":"Table II","truncated":false},{"metric":"Comparison","text":"the Tmax was shorter than that of the reference capsule.","source":"fulltext","location":"Table II / Results p.87","truncated":false}]},{"id":"pmid-17692492","title":"Analysis of silibinin in rat plasma and bile for hepatobiliary excretion and oral bioavailability application.","year":"2007","journal":"Journal of pharmaceutical and biomedical analysis","pmid":"17692492","pmcid":null,"doi":"10.1016/j.jpba.2007.06.026","url":"https://pubmed.ncbi.nlm.nih.gov/17692492/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/17692492/","doiUrl":"https://doi.org/10.1016/j.jpba.2007.06.026","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups i.v. vs oral; no crossover described)","n":"12","formsStudiedRaw":"Silibinin (silybin) isolated from milk thistle (Sigma)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"After silibinin administration in rats, the disposition of silibinin in the plasma and bile fluid was due to rapid distribution and equilibration between the blood and hepatobiliary system, and the bile levels of unconjugated silibinin and total silibinin were greater than those in the plasma. The oral bioavailability of silibinin in rats was estimated to be 0.73%.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Absolute bioavailability","text":"The oral bioavailability of silibinin in rats was estimated to be 0.73%.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Absolute bioavailability","text":"The absolute oral bioavailability of silibinin in rats was calculated to be about 0.95%.","source":"fulltext","location":"Results 3.6 (p.640)","truncated":false},{"metric":"Comparison","text":"the concentrations of silibinin in the bile were higher than those in the blood for the same period of time","source":"fulltext","location":"Results 3.5","truncated":false}]},{"id":"pmid-16275123","title":"Effect of silymarin and its polyphenolic fraction on cholesterol absorption in rats.","year":"2006","journal":"Pharmacological research","pmid":"16275123","pmcid":null,"doi":"10.1016/j.phrs.2005.09.004","url":"https://pubmed.ncbi.nlm.nih.gov/16275123/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/16275123/","doiUrl":"https://doi.org/10.1016/j.phrs.2005.09.004","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel-group animal experiment","n":null,"formsStudiedRaw":"Silymarin and polyphenolic fraction of silymarin (milk thistle)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: off-target analyte (Study of the effect of silymarin/polyphenolic fraction on intestinal absorption of dietary cholesterol in rats (dual-isotope method). Measured analyte is cholesterol, not silymarin; no silymarin/silibinin absorption or PK measured. Cholesterol absorption % is figure-only.)","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The major new finding in this study is that silymarin and its polyphenolic fraction inhibit cholesterol absorption in intestine of rats fed on high cholesterol diet and consequently positively modify lipoprotein cholesterol profile in plasma and content of lipids (cholesterol, TAG) in liver.","source":"fulltext","location":"Discussion (final paragraph, p.8)","truncated":false},{"metric":"Comparison","text":"Silymarin as well as its PF significantly reduced cholesterol absorption.","source":"fulltext","location":"Results 3.2 / Fig. 1","truncated":false},{"metric":"Comparison","text":"Administration of ezetimibe significantly decreased absorption of cholesterol","source":"fulltext","location":"Results 3.2","truncated":false},{"metric":"Comparison","text":"administration of cholestyramine caused no significant change in absorption of dietary cholesterol","source":"fulltext","location":"Results 3.2","truncated":false},{"metric":"Comparison","text":"Feeding of rats on HCD did not influence the cholesterol absorption.","source":"fulltext","location":"Results 3.2","truncated":false}]},{"id":"pmid-16300915","title":"The preparation of silybin-phospholipid complex and the study on its pharmacokinetics in rats.","year":"2006","journal":"International journal of pharmaceutics","pmid":"16300915","pmcid":null,"doi":"10.1016/j.ijpharm.2005.10.001","url":"https://pubmed.ncbi.nlm.nih.gov/16300915/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/16300915/","doiUrl":"https://doi.org/10.1016/j.ijpharm.2005.10.001","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"randomized parallel (two groups) comparison, plus in vitro physicochemical tests","n":"12","formsStudiedRaw":"Silybin (silybin-phospholipid complex vs silybin-N-methylglucamine)","formTags":[],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Drugs and phospholipids of phospholipids complex in vitro had not changed characteristics of themselves, but the combination changed greatly their characteristics in vivo, such as a remarkable enhancement of GI tract absorption.","source":"fulltext","location":"4. Conclusion","truncated":false},{"metric":"AUC","text":"AUC0–∞ 1020.33 and 235.81 ng ml−1 h, respectively","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Tmax","text":"Tmax 10 and 5 min","source":"fulltext","location":"Abstract / Results 3.7","truncated":false},{"metric":"Cmax","text":"average values of Cmax is 126.72 ng ml−1","source":"fulltext","location":"Results 3.7","truncated":false},{"metric":"Cmax","text":"average value of Cmax was 104.29 ng ml−1","source":"fulltext","location":"Results 3.7","truncated":false},{"metric":"Comparison","text":"The bioavailability of silybin in rats was increased remarkably after oral administration of silybin–phospholipid complex comparing to silybin-N-methylglucamine.","source":"fulltext","location":"Table 3 / Abstract","truncated":false},{"metric":"Comparison","text":"silybin-N-methylglucamine is metabolized more rapidly than phospholipids complex with the approximate same Cmax","source":"fulltext","location":"Results 3.7","truncated":false}]},{"id":"pmid-12748991","title":"Plasma lipoproteins in transport of silibinin, an antioxidant flavonolignan from Silybum marianum.","year":"2003","journal":"Phytotherapy research : PTR","pmid":"12748991","pmcid":null,"doi":"10.1002/ptr.1187","url":"https://pubmed.ncbi.nlm.nih.gov/12748991/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/12748991/","doiUrl":"https://doi.org/10.1002/ptr.1187","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":null,"formsStudiedRaw":"Silibinin (silybin) and silibinin-phosphatidylcholine complex (125I-labelled and unlabelled)","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"These results suggest that (i) silibinin is not resorbed by the chylomicron pathway, and (ii) the endogenous lipoprotein pathway VLDL → LDL may play a role in the transport of silibinin from the liver to the extrahepatic tissues concurrently facilitating the lipoprotein antioxidant influence of silibinin.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Tmax","text":"reaching maximal levels within 30-60 min","source":"fulltext","location":"Results p.3","truncated":false},{"metric":"Tmax","text":"the radioactivities reached their maximum levels within 30-60 min","source":"fulltext","location":"Discussion p.4","truncated":false},{"metric":"Tmax","text":"peak levels within 30-60 min indicating rapid tissue distribution","source":"fulltext","location":"Discussion p.6","truncated":false},{"metric":"Comparison","text":"Administration of 125I-SPC resulted in an almost three times higher radioactivity in the blood as well as in the plasma and lipoprotein fractions in comparison with the data obtained after administration of 125I-SB.","source":"fulltext","location":"Results p.3; Table 1","truncated":false},{"metric":"Comparison","text":"Radioactivity in all isolated plasma lipoprotein fractions was proportionally higher after 125I-SPC","source":"fulltext","location":"Results p.3; Table 1","truncated":false},{"metric":"Comparison","text":"olive oil administration produced a slightly decreasing effect on the time courses of radioactivity appearance in the blood and plasma","source":"fulltext","location":"Results p.3; Fig. 1","truncated":false},{"metric":"Comparison","text":"In the LDL fraction the radioactivity level was significantly lower in the olive oil group 30 min after gavage.","source":"fulltext","location":"Results p.3; Fig. 1","truncated":false},{"metric":"Comparison","text":"showed a mild decreasing effect of olive oil administration, particularly at the 60 min interval","source":"fulltext","location":"Results p.3; Fig. 3a; Table 2","truncated":false},{"metric":"Comparison","text":"a p < 0.01 (olive oil vs saline)","source":"fulltext","location":"Table 3","truncated":false}]},{"id":"pmid-11529693","title":"Pharmacokinetic study of iodine-labeled silibinins in rat.","year":"2001","journal":"Pharmacological research","pmid":"11529693","pmcid":null,"doi":"10.1006/phrs.2001.0854","url":"https://pubmed.ncbi.nlm.nih.gov/11529693/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/11529693/","doiUrl":"https://doi.org/10.1006/phrs.2001.0854","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"parallel","n":null,"formsStudiedRaw":"Silibinin (silybin) and silibinin-phosphatidylcholine complex (125I-labeled derivatives)","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"the results of this study suggest that 125I bound to silibinin separated as 125I-SB1 does not significantly change (at least at the low dose of unlabeled silibinin) the properties of labeled silibinin as far as its bioavailability and organ distribution are concerned. Thus, the use of 125I-SB1 should be considered as an option for pharmacokinetic studies of bioavailability of silibinin and its derivatives in experimental animals.","source":"fulltext","location":"Discussion p.6-7","truncated":false},{"metric":"AUC","text":"AUC 257.60 ± 42.69 vs 1382.30 ± 60.20, P< 0.01, and RAmax 2.24 ± 0.68 vs 8.62 ± 0.92, P< 0.01","source":"fulltext","location":"Results p.2","truncated":false},{"metric":"Comparison","text":"only the lower dose of unlabeled silibinin in complex with phosphatidylcholine produced the expected significant increase in AUC and RAmax","source":"fulltext","location":"Results p.2; Fig. 2","truncated":false},{"metric":"Comparison","text":"This dose-response relationship was not observed after 125I-SPC1 administration.","source":"fulltext","location":"Results p.2","truncated":false},{"metric":"Comparison","text":"0.84 ± 0.20 vs 2.12 ± 0.28, P <0.05","source":"fulltext","location":"Results p.2","truncated":false},{"metric":"Comparison","text":"0.52±0.12 vs 1.27±0.12, P< 0.02","source":"fulltext","location":"Results p.2","truncated":false},{"metric":"Comparison","text":"0.63 ± 0.20 vs 1.47 ± 0.21, P< 0.05","source":"fulltext","location":"Results p.3","truncated":false},{"metric":"Comparison","text":"2.44 ± 0.39 vs 1.90 ± 0.55, N.S.","source":"fulltext","location":"Results p.3","truncated":false}]},{"id":"pmid-9008269","title":"Effect of portal vein ligation and silymarin treatment on aspirin metabolism and disposition in rats.","year":"1997","journal":"Biopharmaceutics & drug disposition","pmid":"9008269","pmcid":null,"doi":"10.1002/(sici)1099-081x(199701)18:1<53::aid-bdd3>3.0.co;2-9","url":"https://pubmed.ncbi.nlm.nih.gov/9008269/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/9008269/","doiUrl":"https://doi.org/10.1002/(sici)1099-081x(199701)18:1<53::aid-bdd3>3.0.co;2-9","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (controlled animal study, parallel groups)","n":null,"formsStudiedRaw":"Milk thistle (silymarin) as pretreatment; measured drug = aspirin","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: off-target analyte (Measured analyte is aspirin (total salicylates in plasma, urinary aspirin metabolites) in portal-vein-ligated rats; silymarin was given only as a 7-day pretreatment and was not measured. No silymarin absorption/PK data. Aspirin PK values recorded for reference.)","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Silymarin markedly reversed the alterations found in the PVL group.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Urinary excretion","text":"The cumulative excretions expressed as percentages of the administered dose (mean+SD) were G, 36+2%, SU, 30+2%, GA, 18+2%, and SA, 13+1%.","source":"fulltext","location":"Results p.57 (Aspirin metabolism)","truncated":false},{"metric":"Comparison","text":"The mean half-life in the PVL rats (49.6+2 min) was nearly 1.4-fold higher than in the sham control (35+1.5 min).","source":"fulltext","location":"Table 3","truncated":false},{"metric":"Comparison","text":"The Cmax reached in the PVL group (152+10 mg mL-1) was not significantly different from Cmax in the other groups.","source":"fulltext","location":"Results p.58","truncated":false},{"metric":"Comparison","text":"Silymarin treatment again was effective in reversing Cmax and AUC effects.","source":"fulltext","location":"Results p.59 and Table 3","truncated":false},{"metric":"Comparison","text":"None of the kinetic parameters calculated showed differences between the rats treated with silymarin or CMC only.","source":"fulltext","location":"Results p.59","truncated":false}]},{"id":"pmid-3398694","title":"Silymarin improves metabolism and disposition of aspirin in cirrhotic rats.","year":"1988","journal":"Life sciences","pmid":"3398694","pmcid":null,"doi":"10.1016/0024-3205(88)90309-8","url":"https://pubmed.ncbi.nlm.nih.gov/3398694/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/3398694/","doiUrl":"https://doi.org/10.1016/0024-3205(88)90309-8","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, animal experiment)","n":null,"formsStudiedRaw":"Milk thistle (silymarin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: off-target analyte (Measured compounds are aspirin (ASA) and its salicylate metabolites; silymarin is only the hepatoprotective intervention and its own absorption/levels were not measured. ASA given i.p. in CCl4-cirrhotic rats with/without oral silymarin.)","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The simultaneous administration of silymarin (50 mg/kg of b.w.) along with CCl4 completely prevented all the alterations.","source":"fulltext","location":"Summary","truncated":false},{"metric":"Urinary excretion","text":"cumulative excretions (expressed as % of the dose, mean ± SD)","source":"fulltext","location":"Results p.3 para 1","truncated":false},{"metric":"Comparison","text":"significantly shortened, in the CCl4-cirrhotic animals (19 ± 1.0 min)","source":"fulltext","location":"Results p.3 para 3","truncated":false},{"metric":"Comparison","text":"CCl4-cirrhotic rats showed a virtual lack of the GL in urine which was compensated by the increased amount excreted as GA and SA (p < 0.001)","source":"fulltext","location":"Results p.3 para 1","truncated":false},{"metric":"Comparison","text":"the half-life of ASA was absolutely normal (33 ± 1.2 min)","source":"fulltext","location":"Results p.3 para 3","truncated":false},{"metric":"Comparison","text":"Silymarin completely prevented those changes","source":"fulltext","location":"Results p.3-4; Table I","truncated":false}]},{"id":"pmid-37964172","title":"A comparative study on the preparation and evaluation of solubilizing systems for silymarin.","year":"2024","journal":"Drug delivery and translational research","pmid":"37964172","pmcid":null,"doi":"10.1007/s13346-023-01476-8","url":"https://pubmed.ncbi.nlm.nih.gov/37964172/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/37964172/","doiUrl":"https://doi.org/10.1007/s13346-023-01476-8","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (beagle dog)","design":"randomized crossover","n":"6","formsStudiedRaw":"Milk thistle (silymarin) - solid dispersion, phospholipid complex, cyclodextrin inclusion complex, SMEDDS vs pure silymarin and Legalon®","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Notably, SM-SMEDDS displayed a notably higher in vitro dissolution rate of SM and exhibited a remarkable improvement in the bioavailability of SM compared to SM-SD, SM-PC, SM-SBE-β-CDIC, and even the commercially available product (Legalon®).","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"Relative bioavailability","text":"relative bioavailability of SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS and Legalon® was 2.30-fold, 2.35-fold, 2.44-fold, 6.34-fold, and 2.45-fold higher than that of SM","source":"fulltext","location":"Results 3.5.2","truncated":false},{"metric":"Relative bioavailability","text":"relative bioavailability of SM, SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS was 0.41-fold, 0.94-fold, 0.96-fold, 0.99-fold, and 2.58-fold higher than that of Legalon®","source":"fulltext","location":"Results 3.5.2","truncated":false},{"metric":"Comparison","text":"SM-SMEDDS exhibited a significantly improved Cmax compared to both SM (p < 0.05) and Legalon® (p < 0.05)","source":"fulltext","location":"Results 3.5.2; Table 3","truncated":false},{"metric":"Comparison","text":"SM-SMEDDS can dramatically enhanced the bioavailability of SM, even compared to Legalon® (p < 0.05)","source":"fulltext","location":"Results 3.5.2","truncated":false}]},{"id":"pmid-39079328","title":"Effects of micelle silymarin in corn-soybean meal-based diet on laying hens' performance, egg quality, and blood profile, with comparative assessment of blood absorption rates between powdered and micelle silymarin.","year":"2024","journal":"Poultry science","pmid":"39079328","pmcid":null,"doi":"10.1016/j.psj.2024.104029","url":"https://pubmed.ncbi.nlm.nih.gov/39079328/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/39079328/","doiUrl":"https://doi.org/10.1016/j.psj.2024.104029","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11340492/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (laying hens, Hy-Line Brown)","design":"parallel (two dietary groups), Experiment 2; Experiment 1 was a 3-group dose-response feeding trial","n":"192 hens (Experiment 2); 288 hens (Experiment 1)","formsStudiedRaw":"Milk thistle (silymarin, powder vs micelle-type)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In addition, the incorporation of MS demonstrated higher blood absorption rates compared to powder-type silymarin.","source":"fulltext","location":"Conclusions (p.7)","truncated":false},{"metric":"Comparison","text":"micelletype silymarin showed a higher (p < 0.05) absorption rate compared to the powdered-type silymarin in 2nd, 4th h.","source":"fulltext","location":"Table 5","truncated":false}]},{"id":"pmid-35300217","title":"In vitro Dissolution Testing and Pharmacokinetic Studies of Silymarin Solid Dispersion After Oral Administration to Healthy Pigs.","year":"2022","journal":"Frontiers in veterinary science","pmid":"35300217","pmcid":null,"doi":"10.3389/fvets.2022.815198","url":"https://pubmed.ncbi.nlm.nih.gov/35300217/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/35300217/","doiUrl":"https://doi.org/10.3389/fvets.2022.815198","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8921073/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (pig)","design":"parallel (randomized two groups) plus in vitro dissolution","n":"16","formsStudiedRaw":"Milk thistle (silymarin solid dispersion vs silymarin premix; silybin measured)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The solid dispersion exhibited the higher Cmax and AUC compared to the premix, and that is consistent with in vitro dissolution data.","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"Comparison","text":"The Cmax and AUC0−∞ for the solid dispersion group were both statistically different (p < 0.05) from the premix group.","source":"fulltext","location":"Table 4","truncated":false},{"metric":"Comparison","text":"The Cmax and AUC0−∞ for the solid dispersion group were both statistically different (p < 0.05)","source":"fulltext","location":"Table 4","truncated":false},{"metric":"Comparison","text":"no significant statistical difference was observed for pharmacokinetic parameters ... such as Kel, t1/2, and Tmax","source":"fulltext","location":"Table 4","truncated":false},{"metric":"Comparison","text":"Cmax and AUC in pharmacokinetics were about ×2.9 and ×2.2 that of the premix group","source":"fulltext","location":"Results p.3; Discussion p.5","truncated":false},{"metric":"Comparison","text":"the total released per unit time was 2.5-fold higher (Table 2, Figure 1)","source":"fulltext","location":"Results p.3","truncated":false}]},{"id":"pmid-32654568","title":"Silymarin loaded floating polymer(s) microspheres: characterization, in-vitro/in-vivo evaluation.","year":"2020","journal":"Pharmaceutical development and technology","pmid":"32654568","pmcid":null,"doi":"10.1080/10837450.2020.1795192","url":"https://pubmed.ncbi.nlm.nih.gov/32654568/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/32654568/","doiUrl":"https://doi.org/10.1080/10837450.2020.1795192","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (New Zealand albino rabbit)","design":"parallel (described as 'parallel group study' / 'bio-equivalence study')","n":"6","formsStudiedRaw":"Milk thistle (silymarin; silybin measured)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Formulation of silymarin microspheres using HPMC, EC and blend of them was a successful trial.","source":"fulltext","location":"4. Conclusion","truncated":false},{"metric":"Relative bioavailability","text":"RB% for F24 to commercial capsule was calculated from the ratio AUC 0-24 test to AUC 0-24 reference and found to be 227%","source":"fulltext","location":"Table 10; Abstract; Results 3.x p.9","truncated":false},{"metric":"Cmax","text":"high Cmax (1021.3 ng/ml) and Tmax (6 h)","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"ANOVA of Cmax, Tmax, AUC0-24, AUC0-1, AUMC24-1 showed significant differences between treatment I and F24 (treatment II)","source":"fulltext","location":"Results p.9","truncated":false}]},{"id":"pmid-26669888","title":"In Vitro Release and Bioavailability of Silybin from Micelle-Templated Porous Calcium Phosphate Microparticles.","year":"2016","journal":"AAPS PharmSciTech","pmid":"26669888","pmcid":null,"doi":"10.1208/s12249-015-0460-4","url":"https://pubmed.ncbi.nlm.nih.gov/26669888/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/26669888/","doiUrl":"https://doi.org/10.1208/s12249-015-0460-4","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (beagle dog)","design":"randomized crossover (4 dogs randomly and equally divided into two groups)","n":"4","formsStudiedRaw":"Silybin (milk thistle)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In summary, a novel porous calcium phosphate microparticle based on povidone/sodium cholate/phospholipid mixed micelles was prepared successfully for the first time. The pharmacokinetic study in beagle dogs showed the enhanced oral bioavailability facilitated by the prepared microparticle.","source":"fulltext","location":"Conclusion (p. 1238)","truncated":false},{"metric":"Cmax","text":"Cmax (418.5±23.7 ng mL−1)","source":"fulltext","location":"Table I; Abstract","truncated":false},{"metric":"Relative bioavailability","text":"the relative bioavailability of silybin-loaded calcium phosphate microparticles in contrast with free silybin was about 167.5%","source":"fulltext","location":"Abstract; Results p. 1237","truncated":false},{"metric":"Comparison","text":"418.5±23.7 vs 112.4±8.4 ng mL−1","source":"fulltext","location":"Table I; Discussion","truncated":false},{"metric":"Comparison","text":"the relative bioavailability ... was about 167.5%","source":"fulltext","location":"Results p. 1237","truncated":false},{"metric":"Comparison","text":"no significant difference was found in t1/2 and MRT between the two experimental groups","source":"fulltext","location":"Discussion p. 1237","truncated":false},{"metric":"Comparison","text":"obvious differences ... with respect to the delayed Tmax from 2 to 4 h","source":"fulltext","location":"Discussion p. 1237","truncated":false}]},{"id":"pmid-24495272","title":"In vivo absorption comparison of nanotechnology-based silybin tablets with its water-soluble derivative.","year":"2015","journal":"Drug development and industrial pharmacy","pmid":"24495272","pmcid":null,"doi":"10.3109/03639045.2014.884123","url":"https://pubmed.ncbi.nlm.nih.gov/24495272/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/24495272/","doiUrl":"https://doi.org/10.3109/03639045.2014.884123","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (rat; Beagle dog)","design":"rat: parallel (3 suspensions); dog: randomized crossover (stated as cross-over with 1 week washing period; randomization not stated)","n":"rats 18 (6 per suspension); dogs 6","formsStudiedRaw":"Milk thistle (silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In vivo absorption study in Beagle dogs demonstrated that the bioavailability of silybin from the nanocrystal tablets was comparable with that of its water-soluble salt form in silybin meglumine tablets.","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"Relative bioavailability","text":"no significant difference in absorption rate and extent ... both with a relative bioavailability of 97.8%","source":"fulltext","location":"Results p.557","truncated":false},{"metric":"Comparison","text":"AUC of the two silybin nanosuspension samples (480 nm and 780 nm) increased by 4.9 and 3.6 times (p<0.05)","source":"fulltext","location":"Results p.555","truncated":false},{"metric":"Comparison","text":"There was no difference in Tmax.","source":"fulltext","location":"Results p.555","truncated":false},{"metric":"Comparison","text":"Taking the dose difference into consideration (50 mg versus 35.6 mg), no significant difference in absorption rate and extent was found","source":"fulltext","location":"Results p.557","truncated":false}]},{"id":"pmid-25956049","title":"Comparison of the oral bioavailability of silymarin-loaded lipid nanoparticles with their artificial lipolysate counterparts: implications on the contribution of integral structure.","year":"2015","journal":"International journal of pharmaceutics","pmid":"25956049","pmcid":null,"doi":"10.1016/j.ijpharm.2015.05.005","url":"https://pubmed.ncbi.nlm.nih.gov/25956049/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/25956049/","doiUrl":"https://doi.org/10.1016/j.ijpharm.2015.05.005","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (beagle dog)","design":"randomized crossover (six-period crossover; randomization not stated)","n":"6","formsStudiedRaw":"Silymarin (milk thistle); silybin measured as marker","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The lipid nanoparticles could be transformed into lipolysates by conventional lipolysis procedures. Approximately 80% of the drug could be transferred into the hydrotropic phase. The lipid nanoparticles showed higher oral bioavailability than their lipolysate counterparts, with the bioavailability of lipolysates of NLCs and SLNs being approximately 75% and 60%, respectively. Therefore, we propose that lipolysis is the predominating mechanism governing oral absorption for lipid nanoparticles. The integral structure of the vehicles contributed only trivially to the overall bioavailability.","source":"fulltext","location":"Conclusion (p. 201)","truncated":false},{"metric":"Relative bioavailability","text":"Taking the bioavailability of NLCs as 100%, the calculated relative bioavailability of NLC lipolysates and the SD mixture was 74.86% and 65.71%, while those for SLNs, SLN lipolysates and the SD mixture were 126.9%, 74.29% and 50.86%","source":"fulltext","location":"Results 3.4 (p. 200)","truncated":false},{"metric":"Relative bioavailability","text":"Pharmacokinetics analysis in dogs showed a decrease in bioavailability of 74.86% and 59.09% for lipolysates compared to integral NLCs and SLNs, respectively.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Relative bioavailability","text":"a decrease in bioavailability of 74.86% and 59.09% for lipolysates compared to integral NLCs and SLNs, respectively","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Relative bioavailability","text":"the bioavailability of lipolysates of NLCs and SLNs being approximately 75% and 60%, respectively","source":"fulltext","location":"Conclusion (p. 201)","truncated":false},{"metric":"AUC","text":"1.30 and 1.31 h µg/mL for SLN and NLC lipolysates, respectively (P>0.05)... 2.22 vs. 1.75 h µg/mL","source":"fulltext","location":"Results 3.4 (p. 200)","truncated":false},{"metric":"Relative bioavailability","text":"NLCs > NLCs lipolysates (74.86%) > SMSD–NLCs mixture (65.71%) > SMSD (32.22%)","source":"fulltext","location":"Results 3.4 (p. 200)","truncated":false},{"metric":"Comparison","text":"0.83 ± 0.33* vs 1.27 ± 0.38; * P < 0.05, compared with SM–NLC","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"1.31 ± 0.49 (no asterisk) vs 1.75 ± 0.47","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"After breaking the mixture down into lipolysates, the oral bioavailability of both SLNs and NLCs decreased (P < 0.05)","source":"fulltext","location":"Table 1; Results 3.4","truncated":false}]},{"id":"pmid-21666703","title":"Proliposomes for oral delivery of dehydrosilymarin: preparation and evaluation in vitro and in vivo.","year":"2011","journal":"Acta pharmacologica Sinica","pmid":"21666703","pmcid":null,"doi":"10.1038/aps.2011.25","url":"https://pubmed.ncbi.nlm.nih.gov/21666703/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/21666703/","doiUrl":"https://doi.org/10.1038/aps.2011.25","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4003120/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (rabbit)","design":"parallel","n":"6","formsStudiedRaw":"Dehydrosilymarin (oxidized derivative of milk thistle silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: off-target analyte (PK/absorption of dehydrosilymarin (a synthetic oxidized derivative of silymarin) measured as dehydrosilybin in rabbit plasma; not silymarin itself (authors could not detect drug after silymarin at the same dose). Data extracted for reference.)","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Proliposomes may be a useful vehicle for oral delivery of dehydrosilymarin, a drug poorly soluble in water.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"Cmax was approximately 0.57 μg/mL","source":"fulltext","location":"Results p.976-977","truncated":false},{"metric":"Cmax","text":"the value of Cmax was approximately 2.83 μg/mL","source":"fulltext","location":"Results p.976-977","truncated":false},{"metric":"Relative bioavailability","text":"the relative bioavailability of proliposomes versus suspension in rabbits was 228.85%","source":"fulltext","location":"Abstract; Results p.977","truncated":false},{"metric":"Comparison","text":"the Cmax was approximately 4.96-fold higher than that of the dehydrosilymarin suspension","source":"fulltext","location":"Results p.977","truncated":false},{"metric":"Comparison","text":"The AUCt of the vesicle was approximately 2.29-fold higher than that of the dehydrosilymarin suspension","source":"fulltext","location":"Results p.977","truncated":false},{"metric":"Comparison","text":"we failed to detect the existence of the drug after oral administration of the same dosage of silymarin","source":"fulltext","location":"Discussion p.979","truncated":false}]},{"id":"pmid-21948306","title":"Silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices: physical characterization and enhanced oral bioavailability.","year":"2011","journal":"AAPS PharmSciTech","pmid":"21948306","pmcid":null,"doi":"10.1208/s12249-011-9666-2","url":"https://pubmed.ncbi.nlm.nih.gov/21948306/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/21948306/","doiUrl":"https://doi.org/10.1208/s12249-011-9666-2","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3225519/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (beagle dog)","design":"randomized crossover (three-period, three formulations)","n":"6","formsStudiedRaw":"Milk thistle (silymarin, measured as silybin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Pharmacokinetic study showed significantly increased peak concentration for silymarin GMO/P407 LCM, and, most importantly, a 3.5-fold increase in silymarin oral bioavailability as compared with Legalon, a commercial silymarin formulation.","source":"fulltext","location":"Conclusions (p.1239)","truncated":false},{"metric":"Relative bioavailability","text":"The relative bioavailability of GMO/P407 LCM and liquid crystalline gel was 345.57% and 367.9%, respectively, with Legalon as the reference","source":"fulltext","location":"Table I; Results p.1239","truncated":false},{"metric":"Comparison","text":"*P<0.05 vs. Legalon","source":"fulltext","location":"Table I","truncated":false},{"metric":"Comparison","text":"significantly increased peak concentration for silymarin GMO/P407 LCM","source":"fulltext","location":"Table I","truncated":false},{"metric":"Comparison","text":"the bioavailability of silymarin after administration of GMO/P407 LCM had no significant difference with liquid crystalline gel (P> 0.05)","source":"fulltext","location":"Results p.1239","truncated":false},{"metric":"Comparison","text":"**P<0.05 vs. liquid crystalline gel","source":"fulltext","location":"Table I","truncated":false}]},{"id":"pmid-20405254","title":"Development of silymarin self-microemulsifying drug delivery system with enhanced oral bioavailability.","year":"2010","journal":"AAPS PharmSciTech","pmid":"20405254","pmcid":null,"doi":"10.1208/s12249-010-9432-x","url":"https://pubmed.ncbi.nlm.nih.gov/20405254/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/20405254/","doiUrl":"https://doi.org/10.1208/s12249-010-9432-x","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2902333/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (mongrel dog)","design":"randomized crossover","n":"6","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In in vivo studies for clinical purpose, SMEDDS showed significantly enhanced absorption than Legalon®.","source":"fulltext","location":"Conclusion p.678","truncated":false},{"metric":"Relative bioavailability","text":"the relative bioavailability of SMEDDS to Legalon® was 227%","source":"fulltext","location":"Results p.677; Abstract (about 2.2-fold)","truncated":false},{"metric":"Comparison","text":"There existed significant difference in Cmax for the two formulations (p<0.05)","source":"fulltext","location":"Results p.677; Table II","truncated":false},{"metric":"Comparison","text":"SMEDDS significantly enhanced the values of AUC0–12 h and Cmax","source":"fulltext","location":"Table II","truncated":false},{"metric":"Comparison","text":"no significant difference was observed (p>0.05) for the two formulations","source":"fulltext","location":"Results p.677","truncated":false}]},{"id":"pmid-20523347","title":"Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles.","year":"2010","journal":"Acta pharmacologica Sinica","pmid":"20523347","pmcid":null,"doi":"10.1038/aps.2010.55","url":"https://pubmed.ncbi.nlm.nih.gov/20523347/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/20523347/","doiUrl":"https://doi.org/10.1038/aps.2010.55","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4002977/","pdfLink":null,"openAccess":"open access: yes (free in PMC)","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (dog)","design":"randomized crossover (described as three-way crossover with two formulations; 2 weeks washout)","n":"6","formsStudiedRaw":"Milk thistle (silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Sodium cholate/phospholipid-mixed micelles are promising carriers in orally delivery of silybin, considering their capability of enhancing bioavailability and large-scale production.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"The Cmax values were 118.9 and 113.3 ng/mL for silybin-sodium cholate/phospholipid-mixed micelles and silybin-N-methylglucamine","source":"fulltext","location":"Results p.763","truncated":false},{"metric":"Relative bioavailability","text":"relative bioavailability of mixed micelles versus silybin-N-methylglucamine in dogs was 252.0%","source":"fulltext","location":"Abstract; Results p.763","truncated":false},{"metric":"Comparison","text":"No significant difference was found in Cmax and Tmax values","source":"fulltext","location":"Results p.763","truncated":false},{"metric":"Comparison","text":"The plasma AUC0–∞ for mixed micelles (1372.4 h·ng/mL) was approximately 2.7-fold greater than that for silybin-N-methylglucamine (505.8 h·ng/mL)","source":"fulltext","location":"Results p.763","truncated":false},{"metric":"Comparison","text":"The silybin-N-methylglucamine exhibited faster release than the silybin-sodium cholate/phospholipid-mixed micelles at all the pH ranges evaluated","source":"fulltext","location":"Discussion p.762-763","truncated":false}]},{"id":"pmid-20621458","title":"Nanostructured lipid carriers for parenteral delivery of silybin: Biodistribution and pharmacokinetic studies.","year":"2010","journal":"Colloids and surfaces. B, Biointerfaces","pmid":"20621458","pmcid":null,"doi":"10.1016/j.colsurfb.2010.06.008","url":"https://pubmed.ncbi.nlm.nih.gov/20621458/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/20621458/","doiUrl":"https://doi.org/10.1016/j.colsurfb.2010.06.008","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (New Zealand rabbit; Kunming mouse)","design":"other (parallel two-group, IV formulation comparison)","n":"8 rabbits; mice NR total","formsStudiedRaw":"Milk thistle (silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"These results indicate that NLC is a potential sustained release and targeting system for silybin.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"silybin-NLC had a 2-fold increase in AUC value compared with the control solution","source":"fulltext","location":"Table 1; Results p.217","truncated":false},{"metric":"Comparison","text":"there was no significant difference between silybin-NLC and silybin solution (P > 0.05)","source":"fulltext","location":"Table 1","truncated":false}]},{"id":"pmid-17348898","title":"Bioavailability of a silybin-phosphatidylcholine complex in dogs.","year":"2007","journal":"Journal of veterinary pharmacology and therapeutics","pmid":"17348898","pmcid":null,"doi":"10.1111/j.1365-2885.2007.00834.x","url":"https://pubmed.ncbi.nlm.nih.gov/17348898/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/17348898/","doiUrl":"https://doi.org/10.1111/j.1365-2885.2007.00834.x","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (dog, beagle)","design":"other (parallel design with day-7 switch of test articles in group B; group A silymarin on day 7 after 6-day washout)","n":"16","formsStudiedRaw":"Silybin-phosphatidylcholine complex (phytosome) vs standardized silymarin extract (milk thistle)","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"This study clearly shows that oral administration of silybin in a phosphatidylcholine complex (phytosome) results in greater bioavailability of silybin compared with standard silymarin extract.","source":"fulltext","location":"Discussion p.137","truncated":false},{"metric":"Cmax","text":"Cmax (ng/mL) 449 ± 402*","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Cmax","text":"Cmax (ng/mL) 472 ± 383*","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Cmax","text":"Cmax (ng/mL) 1310 ± 880*","source":"fulltext","location":"Table 1; Abstract","truncated":false},{"metric":"Tmax","text":"Tmax (h) 6.87 ± 7.43","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Tmax","text":"Tmax (h) 4.75 ± 2.82","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Tmax","text":"Tmax (h) 2.87 ± 2.23","source":"fulltext","location":"Table 1","truncated":false},{"metric":"AUC","text":"AUC0-24 (ng·h/mL) 2520 ± 2976*","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"*P < 0.05 between silymarin extract groups and SPC group.","source":"fulltext","location":"Table 1","truncated":false},{"metric":"Comparison","text":"There was no statistically significant difference in the Tmax values between the SPC and silymarin extract group of dogs.","source":"fulltext","location":"Results p.134","truncated":false}]},{"id":"pmid-16527467","title":"Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system.","year":"2006","journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V","pmid":"16527467","pmcid":null,"doi":"10.1016/j.ejpb.2005.12.005","url":"https://pubmed.ncbi.nlm.nih.gov/16527467/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/16527467/","doiUrl":"https://doi.org/10.1016/j.ejpb.2005.12.005","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (rabbit)","design":"randomized crossover (SMEDDS vs PEG 400 solution, 6 rabbits, 7-day washout); separate preliminary evaluation of suspension in 6 rabbits","n":null,"formsStudiedRaw":"Silymarin (SMEDDS, PEG 400 solution, suspension); silybin measured","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Relative bioavailability of silymarin SMEDDS was dramatically enhanced, approximately 1.88- and 48.82-fold that of silymarin PEG 400 solution and suspension, respectively. It was concluded that alternative mechanisms other than improved release contribute to enhancement of bioavailability of silymarin.","source":"fulltext","location":"4. Conclusion","truncated":false},{"metric":"AUC","text":"with AUC0–16h of only 0.11 lg h/ml","source":"fulltext","location":"Results 3.4","truncated":false},{"metric":"Relative bioavailability","text":"mean relative bioavailability of silymarin SMEDDS was 1.88- and 48.82-fold that of silymarin PEG 400 solution and suspension","source":"fulltext","location":"Abstract / Results 3.4","truncated":false},{"metric":"Relative bioavailability","text":"1.88- and 48.82-fold that of silymarin PEG 400 solution and suspension","source":"fulltext","location":"Abstract / Results 3.4","truncated":false},{"metric":"Comparison","text":"Relative bioavailability of SMEDDS was dramatically enhanced in an average of 1.88- and 48.82-fold that of silymarin PEG 400 solution and suspension, respectively.","source":"fulltext","location":"Abstract / Results 3.4","truncated":false}]},{"id":"pmid-16687221","title":"Preparation of silymarin proliposome: a new way to increase oral bioavailability of silymarin in beagle dogs.","year":"2006","journal":"International journal of pharmaceutics","pmid":"16687221","pmcid":null,"doi":"10.1016/j.ijpharm.2006.03.037","url":"https://pubmed.ncbi.nlm.nih.gov/16687221/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/16687221/","doiUrl":"https://doi.org/10.1016/j.ijpharm.2006.03.037","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"other_animal","speciesRaw":"other animal (beagle dog)","design":"randomized parallel (two groups of 6)","n":"12","formsStudiedRaw":"Silymarin (proliposome vs capsule)","formTags":["enhanced"],"food":true,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Silymarin proliposome was stable and did enchance the gastrointestinal absorption of silymarin.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Cmax","text":"average value of Cmax was 472.62 ng ml-1 after oral administration of liposomal suspensions","source":"fulltext","location":"Abstract / Results 3.7","truncated":false},{"metric":"Cmax","text":"average value of Cmax was 89.78 ng ml-1 after oral administration of the capsule full of silymarin","source":"fulltext","location":"Abstract / Results 3.7","truncated":false},{"metric":"Tmax","text":"Tmax both 30 min","source":"fulltext","location":"Abstract / Results 3.7","truncated":false},{"metric":"AUC","text":"AUC0-∞ 2606.21 and 697 ng mL-1 h, respectively","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"The high bioavailability of silymarin proliposome could be obtained by oral administration.","source":"fulltext","location":"Abstract / Tables 2-3","truncated":false}]},{"id":"pmid-40992023","title":"A hepatocyte targeted silymarin sea cucumber peptide-galactose nanoparticle for the alleviation of ethanol-induced damage in cells.","year":"2026","journal":"Colloids and surfaces. B, Biointerfaces","pmid":"40992023","pmcid":null,"doi":"10.1016/j.colsurfb.2025.115152","url":"https://pubmed.ncbi.nlm.nih.gov/40992023/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/40992023/","doiUrl":"https://doi.org/10.1016/j.colsurfb.2025.115152","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation and cell study)","n":null,"formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Collectively, these findings highlight the promise of Gal-glycosylated SCP-based nanoparticles as an effective system for targeted delivery of silymarin, providing substantial protection against ethanol-induced cellular injury.","source":"fulltext","location":"Conclusion (section 4)","truncated":false}]},{"id":"pmid-41722252","title":"Silibinin-loaded PEGylated niosomal nanoparticles restore hippocampus histological changes, memory and learning, and downregulate the inflammasome pathway in Alzheimer's disease animal models.","year":"2026","journal":"Biochemical and biophysical research communications","pmid":"41722252","pmcid":null,"doi":"10.1016/j.bbrc.2026.153496","url":"https://pubmed.ncbi.nlm.nih.gov/41722252/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/41722252/","doiUrl":"https://doi.org/10.1016/j.bbrc.2026.153496","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro release plus animal efficacy study)","n":"40 rats (efficacy study)","formsStudiedRaw":"Milk thistle (silibinin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"These findings suggest that PEGylated Silibinin-loaded niosomal nanoparticles are an effective option for improving Alzheimer's disease complications by modulating the inflammasome pathway and amyloid plaque aggregation.","source":"fulltext","location":"Abstract","truncated":false}]},{"id":"pmid-41729747","title":"In vitro and ex vivo Cutaneous Bioavailability and Biotransformation of Silymarin and Its Constituents.","year":"2026","journal":"Skin pharmacology and physiology","pmid":"41729747","pmcid":null,"doi":"10.1159/000550859","url":"https://pubmed.ncbi.nlm.nih.gov/41729747/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/41729747/","doiUrl":"https://doi.org/10.1159/000550859","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro and ex vivo uptake and biotransformation study)","n":null,"formsStudiedRaw":"Milk thistle (silymarin and constituents: silybin, isosilybin, 2,3-dehydrosilybin, silychristin, silydianin, taxifolin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Here, we found that polyphenol constituents of SM penetrate into human skin cells and tissue depending on their lipophilicity [28]. In skin fibroblasts and tissue, they are converted into various metabolites.","source":"fulltext","location":"Conclusion (p.18)","truncated":false},{"metric":"Comparison","text":"the content of studied substances in NHDF was in the order DHSB>ISB>SB","source":"fulltext","location":"Results p.5; Discussion p.17","truncated":false},{"metric":"Comparison","text":"DHSB>ISB>SB>SC>SD>TA","source":"fulltext","location":"Abstract; Results p.8","truncated":false},{"metric":"Comparison","text":"SB entered NHDF significantly less than DHSB (Tables 2-4)","source":"fulltext","location":"Results p.5","truncated":false}]},{"id":"pmid-42660255","title":"Co-delivery of doxorubicin and silybin via taurine-conjugated chitosan-modified TAUT-targeted liposomes enhances oral bioavailability and alleviates doxorubicin-induced cardiomyocyte toxicity in vitro.","year":"2026","journal":"International journal of biological macromolecules","pmid":"42660255","pmcid":null,"doi":"10.1016/j.ijbiomac.2026.154244","url":"https://pubmed.ncbi.nlm.nih.gov/42660255/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/42660255/","doiUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154244","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (formulation study)","n":null,"formsStudiedRaw":"Milk thistle (silybin, co-loaded with doxorubicin in TAU-CS-coated liposomes)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Collectively, these findings establish taurine transporter (TAUT)-targeted DOX/SLB co-loaded liposomes as an oral delivery platform that enhances DOX systemic exposure through intestinal uptake and metabolic-barrier modulation while reducing DOX-induced cardiomyocyte toxicity in vitro.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"TAU-CS-coated liposomes exhibited a significantly slower release profile","source":"fulltext","location":"Results 3.3","truncated":false}]},{"id":"pmid-38794280","title":"Evaluation of Silybin Nanoparticles against Liver Damage in Murine Schistosomiasis mansoni Infection.","year":"2024","journal":"Pharmaceutics","pmid":"38794280","pmcid":null,"doi":"10.3390/pharmaceutics16050618","url":"https://pubmed.ncbi.nlm.nih.gov/38794280/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/38794280/","doiUrl":"https://doi.org/10.3390/pharmaceutics16050618","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11125168/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (formulation development, in vitro permeability/release, in vivo efficacy)","n":null,"formsStudiedRaw":"Milk thistle (silybin; silymarin as comparator)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In conclusion, SLN-SIB-U represents a promising nanosystem for enhancing the pharmacokinetic properties of SIB considering the 3Rs approach.","source":"fulltext","location":"Conclusions (p.20)","truncated":false},{"metric":"Comparison","text":"SLN-SIB-U, which presented Papp values greater than those of PN-SIB and two times greater than those of SIB.","source":"fulltext","location":"Fig. 6C; Results 3.3.2","truncated":false},{"metric":"Comparison","text":"the Papp of SIB was greater than that of Sili","source":"fulltext","location":"Fig. 6C","truncated":false},{"metric":"Comparison","text":"PN-SIB exhibited faster release of SIB under physiological conditions than SLN (p < 0.0001).","source":"fulltext","location":"Results 3.2.2 p.13","truncated":false}]},{"id":"pmid-39344123","title":"Potential of CME@ZIF-8 MOF Nanoformulation: Smart Delivery of Silymarin for Enhanced Performance and Mechanism in Albino Rats.","year":"2024","journal":"ACS applied bio materials","pmid":"39344123","pmcid":null,"doi":"10.1021/acsabm.4c01019","url":"https://pubmed.ncbi.nlm.nih.gov/39344123/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/39344123/","doiUrl":"https://doi.org/10.1021/acsabm.4c01019","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro; albino rats","design":"in vitro release study; parallel-group rat efficacy study","n":null,"formsStudiedRaw":"Silymarin (PEG-Sily@CME@ZIF-8 MOF nanoformulation)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"This study showed how important CME@ZIF-8 MOFs are for boosting silymarin's absorption, solubility, and in vivo nephron-cardioprotective benefits.","source":"fulltext","location":"Conclusion","truncated":false}]},{"id":"pmid-36985575","title":"Preparation, Characterization and Evaluation of Flavonolignan Silymarin Effervescent Floating Matrix Tablets for Enhanced Oral Bioavailability.","year":"2023","journal":"Molecules (Basel, Switzerland)","pmid":"36985575","pmcid":null,"doi":"10.3390/molecules28062606","url":"https://pubmed.ncbi.nlm.nih.gov/36985575/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/36985575/","doiUrl":"https://doi.org/10.3390/molecules28062606","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10054735/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"other animal (albino rabbit); human volunteers only for ultrasound floating study; in vitro dissolution","design":"parallel","n":null,"formsStudiedRaw":"Milk thistle (silymarin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The silymarin gastro-retentive formulation achieved an improved area under the curve, longer MRT, and longer half-life as compared to the conventional formulation in rabbits.","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"Cmax","text":"Cmax for the conventional form was 0.6 ± 0.11 µg mL−1","source":"fulltext","location":"Table 5","truncated":false},{"metric":"Cmax","text":"it was 1.1 ± 0.42 µg mL−1 for the formulation","source":"fulltext","location":"Table 5","truncated":false},{"metric":"Comparison","text":"The conventional form and the formulation varied significantly (p < 0.05), according to a statistical analysis employing a t-test.","source":"fulltext","location":"Results 2.10","truncated":false}]},{"id":"pmid-37342048","title":"In-silico, in-vitro and ex-vivo evidence of combining silymarin phytopharmaceutical with piperine, and fulvic acid for enhancing its solubility and permeability.","year":"2023","journal":"Pharmaceutical development and technology","pmid":"37342048","pmcid":null,"doi":"10.1080/10837450.2023.2227966","url":"https://pubmed.ncbi.nlm.nih.gov/37342048/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/37342048/","doiUrl":"https://doi.org/10.1080/10837450.2023.2227966","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in silico + in vitro + ex vivo)","n":null,"formsStudiedRaw":"Milk thistle (silymarin phytopharmaceutical, 80% MT extract-derived; with piperine and fulvic acid)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Thus, the use of described BEs had in turns increased the BA of SM and might have the probability of increasing the NAFLD activity.","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"Comparison","text":"These results demonstrated that with the addition of BEs in the SM PP there is an increase in drug release","source":"fulltext","location":"Results 4.5.3","truncated":false},{"metric":"Comparison","text":"significantly higher as compared to the SM suspension (1.63 × 10^6 cm/s) and SM marketed formulation (3.11 × 10^6 cm/s)","source":"fulltext","location":"Results 4.6.1","truncated":false},{"metric":"Comparison","text":"The marketed formulation and SM PP have almost similar BA fraction","source":"fulltext","location":"Results 4.5.3; Discussion","truncated":false}]},{"id":"pmid-38144097","title":"Designing a Silymarin Nanopercolating System Using CME@ZIF-8: An Approach to Hepatic Injuries.","year":"2023","journal":"ACS omega","pmid":"38144097","pmcid":null,"doi":"10.1021/acsomega.3c08494","url":"https://pubmed.ncbi.nlm.nih.gov/38144097/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/38144097/","doiUrl":"https://doi.org/10.1021/acsomega.3c08494","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10734040/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (formulation development; in vitro release plus rat CCl4 hepatotoxicity model)","n":"28 rats (in vivo study); in vitro NR","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Ultimately, our findings highlight the effectiveness of CME@ZIF-8-based silymarin (nanosilymarin) in enhancing the pharmacological effects of the poorly soluble medication silymarin by increasing its solubility and bioavailability.","source":"fulltext","location":"Conclusions (p.48544)","truncated":false},{"metric":"Comparison","text":"The drug release rates from PEG-SIly@CME@ZIF-8 are slower at pH 7.4 than they are at pH 5.","source":"fulltext","location":"Results 2.3","truncated":false}]},{"id":"pmid-35214124","title":"Hydroxypropyl-β-cyclodextrin Enhances Oral Absorption of Silymarin Nanoparticles Prepared Using PureNano™ Continuous Crystallizer.","year":"2022","journal":"Pharmaceutics","pmid":"35214124","pmcid":null,"doi":"10.3390/pharmaceutics14020394","url":"https://pubmed.ncbi.nlm.nih.gov/35214124/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/35214124/","doiUrl":"https://doi.org/10.3390/pharmaceutics14020394","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8880042/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation characterisation)","n":null,"formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"We revealed that HP-β-CyD was a potential cryoprotectant in NP formulation using an SLM nano-suspension prepared by PureNano. SLM/HPMC/HP-β-CyD NPs showed good redispersion ability and rapid dissolution rate, probably due to the complex formation with SLM.","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"Comparison","text":"significantly enhanced (108 ± 6.0 µg/mL, compared to that of SLM/HPMC/Ery NPs or SLM/HPMC/α-CyD NPs","source":"fulltext","location":"Section 3.4; Fig. 4","truncated":false},{"metric":"Comparison","text":"Poor membrane permeability was observed in the original SLM powder","source":"fulltext","location":"Sections 3.3, 3.5","truncated":false},{"metric":"Comparison","text":"the membrane permeability of SLM/HPMC/HP-β-CyD NPs was slightly lower than that of SLM/NPMC/Ery NPs","source":"fulltext","location":"Section 3.5","truncated":false}]},{"id":"pmid-34695708","title":"Investigation on the solid-phase synthesis of silybin prodrugs and their timed-release.","year":"2021","journal":"Bioorganic & medicinal chemistry","pmid":"34695708","pmcid":null,"doi":"10.1016/j.bmc.2021.116478","url":"https://pubmed.ncbi.nlm.nih.gov/34695708/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/34695708/","doiUrl":"https://doi.org/10.1016/j.bmc.2021.116478","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro chemical/enzymatic stability study)","n":null,"formsStudiedRaw":"Milk thistle (silibinin / silybin A / silybin B prodrugs)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Uridine-silybin prodrugs were quickly cleaved by RNase A, releasing the active silybin drugs even at low RNase concentrations.","source":"fulltext","location":"Conclusions p.4","truncated":false},{"metric":"Comparison","text":"uridine derivatives are cleaved much faster than compounds derivatized with adenosine","source":"fulltext","location":"Results p.4","truncated":false},{"metric":"Comparison","text":"The cleavage of the 12b derivative (SilB-p-Ur) is slightly faster than 12ab and 12a","source":"fulltext","location":"Results p.4","truncated":false},{"metric":"Comparison","text":"New conjugates were much more water soluble than silibinin","source":"fulltext","location":"Results p.3","truncated":false}]},{"id":"pmid-34944582","title":"Preparation and Characterization of Silymarin-Conjugated Gold Nanoparticles with Enhanced Anti-Fibrotic Therapeutic Effects against Hepatic Fibrosis in Rats: Role of MicroRNAs as Molecular Targets.","year":"2021","journal":"Biomedicines","pmid":"34944582","pmcid":null,"doi":"10.3390/biomedicines9121767","url":"https://pubmed.ncbi.nlm.nih.gov/34944582/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/34944582/","doiUrl":"https://doi.org/10.3390/biomedicines9121767","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8698929/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (formulation characterisation + in vitro release + in vivo pharmacodynamic rat study)","n":"30 rats (in vivo part)","formsStudiedRaw":"Milk thistle (silymarin) - silymarin-conjugated gold nanoparticles (SGNPs)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"We successfully synthesized SIL-loaded GNPs (SGNPs) with sizes ranging from 16 up to 20 nm, entrapment efficiency 96%, and loading capacity 38.69%. The in vivo study indicated that the obtained nano-formulation of SIL boosts its anti-fibrotic effects.","source":"fulltext","location":"Conclusions (Section 5)","truncated":false},{"metric":"Comparison","text":"the higher the concentration is, the higher the encapsulation efficiency is","source":"fulltext","location":"Section 3.2.5; Table 2","truncated":false}]},{"id":"pmid-35300372","title":"Synthesis of silymarin-selenium nanoparticle conjugate and examination of its biological activity in vitro.","year":"2021","journal":"ADMET & DMPK","pmid":"35300372","pmcid":null,"doi":"10.5599/admet.1023","url":"https://pubmed.ncbi.nlm.nih.gov/35300372/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/35300372/","doiUrl":"https://doi.org/10.5599/admet.1023","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8920099/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro nanoparticle synthesis and cell assays)","n":null,"formsStudiedRaw":"Milk thistle (silymarin) conjugated to selenium nanoparticles (Se/Sil)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Thus, SeNPs are promising for use as a Sil carrier and as protective antigens.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"Because there was no fluorescence when Sil acted alone, one can speculate that SeNPs are crucial for the Sil penetration of the cells.","source":"fulltext","location":"Results p.262","truncated":false}]},{"id":"pmid-33237069","title":"Hydrophilic co-assemblies of two hydrophobic biomolecules improving the bioavailability of silybin.","year":"2020","journal":"Food & function","pmid":"33237069","pmcid":null,"doi":"10.1039/d0fo01882a","url":"https://pubmed.ncbi.nlm.nih.gov/33237069/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/33237069/","doiUrl":"https://doi.org/10.1039/d0fo01882a","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation characterisation and cell assays)","n":null,"formsStudiedRaw":"Silybin (milk thistle), loaded in wheat gluten protein-shellac co-assemblies (WSCs)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Moreover, the encapsulation effectively improved the bioavailability of silybin by up to 50%.","source":"fulltext","location":"Conclusions","truncated":false},{"metric":"Comparison","text":"The cytotoxicity of silybin loaded in WSCs was stronger than that dissolved in DMSO ( p < 0.05)","source":"fulltext","location":"Results, Cell assays; Fig. 7F","truncated":false},{"metric":"Comparison","text":"The apoptosis rates of HepG-2 cells treated with silybin loaded WSCs were all higher than that treated with free silybin in DMSO.","source":"fulltext","location":"Discussion; Fig. 8","truncated":false}]},{"id":"pmid-30448315","title":"Formulation and biopharmaceutical evaluation of supersaturatable self-nanoemulsifying drug delivery systems containing silymarin.","year":"2019","journal":"International journal of pharmaceutics","pmid":"30448315","pmcid":null,"doi":"10.1016/j.ijpharm.2018.11.036","url":"https://pubmed.ncbi.nlm.nih.gov/30448315/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/30448315/","doiUrl":"https://doi.org/10.1016/j.ijpharm.2018.11.036","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"other animal (rabbit; also in vitro; mouse pharmacodynamics not extracted)","design":"parallel","n":"9 (4 Legalon + 5 S-SNEDDS)","formsStudiedRaw":"Milk thistle (silymarin; measured as silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The combination of two techniques including SNEDDS and addition of 10% of Poloxamer 407 remarkably increased DE4h (88.28%) compared to the reference product (6.41%). The relative bioavailability of S-SNEDDS versus Legalon® was about 760%.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Relative bioavailability","text":"The relative bioavailability of S-SNEDDS versus Legalon® was about 760%.","source":"fulltext","location":"Table 3; Abstract","truncated":false},{"metric":"Relative bioavailability","text":"oral bioavailability of silybin after administration of S-SNEDDS (7.6 folds) compared to Legalon","source":"fulltext","location":"Discussion (p.74)","truncated":false},{"metric":"Comparison","text":"S-SNEDDS significantly improved the relative bioavailability of silybin compared to the branded product.","source":"fulltext","location":"Table 3; Results 4.3","truncated":false},{"metric":"Comparison","text":"the combination of SNEDDS and a precipitation inhibitor in S-SNEDDS also markedly increased the maximum concentration of silybin","source":"fulltext","location":"Table 3","truncated":false}]},{"id":"pmid-30502425","title":"Design, optimization and in vitro-in vivo evaluation of smart nanocaged carrier delivery of multifunctional PEG-chitosan stabilized silybin nanocrystals.","year":"2019","journal":"International journal of biological macromolecules","pmid":"30502425","pmcid":null,"doi":"10.1016/j.ijbiomac.2018.11.258","url":"https://pubmed.ncbi.nlm.nih.gov/30502425/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/30502425/","doiUrl":"https://doi.org/10.1016/j.ijbiomac.2018.11.258","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"other animal (rabbit); also in vitro","design":"parallel","n":"9","formsStudiedRaw":"Milk thistle (silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"the nanocaged nanocrystals technology with excellent stability, improved dissolution velocity and relative bioavailability was recommended as an efficient and feasible approach for water insoluble drugs delivery.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Relative bioavailability","text":"nanocaged nanocrystals and the PEG-CS nanocrystals drug delivery system also exhibited 5.54 and 2.58 fold increasing in the AUC","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Relative bioavailability","text":"5.54 and 2.58 fold increasing in the AUC, respectively","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Relative bioavailability","text":"AUC of the nanocaged nanocrystals significantly increased by 2.1 times and 5.5 times compared to the silybin solution and the PEG-CS nanocrystals, respectively","source":"fulltext","location":"Results 3.11","truncated":false},{"metric":"Relative bioavailability","text":"increased by 2.1 times and 5.5 times compared to the silybin solution and the PEG-CS nanocrystals, respectively","source":"fulltext","location":"Results 3.11","truncated":false},{"metric":"Comparison","text":"AUC of the nanocaged nanocrystals significantly increased by 2.1 times and 5.5 times compared to the silybin solution and the PEG-CS nanocrystals, respectively (P < 0.05)","source":"fulltext","location":"Results 3.11","truncated":false}]},{"id":"pmid-30935093","title":"Intestinal Permeability Study of Clinically Relevant Formulations of Silibinin in Caco-2 Cell Monolayers.","year":"2019","journal":"International journal of molecular sciences","pmid":"30935093","pmcid":null,"doi":"10.3390/ijms20071606","url":"https://pubmed.ncbi.nlm.nih.gov/30935093/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/30935093/","doiUrl":"https://doi.org/10.3390/ijms20071606","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6480586/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro permeability)","n":null,"formsStudiedRaw":"Milk thistle (silibinin formulations)","formTags":["phytosome"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Our approach predicted differential mechanisms of transport and blood–brain barrier permeabilities between the silibinin formulations tested.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Comparison","text":"* One-way ANOVA p < 0.0001","source":"fulltext","location":"Fig. 1B legend","truncated":false},{"metric":"Comparison","text":"was 1.57 (<2), significantly lower than that obtained with silibinin-PC","source":"fulltext","location":"Fig. 2A; Results p.3","truncated":false}]},{"id":"pmid-31052197","title":"Formulation of Nanomicelles to Improve the Solubility and the Oral Absorption of Silymarin.","year":"2019","journal":"Molecules (Basel, Switzerland)","pmid":"31052197","pmcid":null,"doi":"10.3390/molecules24091688","url":"https://pubmed.ncbi.nlm.nih.gov/31052197/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/31052197/","doiUrl":"https://doi.org/10.3390/molecules24091688","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6540123/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation characterization)","n":null,"formsStudiedRaw":"Milk thistle (silymarin, nanomicelle formulations)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"PAMPA demonstrated that PNM and MNM enhanced the passive diffusion of SLM. Based on the cellular results, nanomicelles have a significant inhibitory effect on the P-gp-mediated efflux of SLM, and MNM increased SLM permeability through Caco-2 cells' monolayer compared to unformulated extract and PNM.","source":"fulltext","location":"Conclusions (section 4)","truncated":false},{"metric":"Comparison","text":"* p < 0.05 vs. SLM-PNM by Mann Whitney test","source":"fulltext","location":"Table 7","truncated":false},{"metric":"Comparison","text":"the efflux ratio for SLM-MNM was significantly lower compared to SLM-PNM","source":"fulltext","location":"Table 7","truncated":false},{"metric":"Comparison","text":"** p < 0.01 vs. free-SLM","source":"fulltext","location":"Fig. 4; Results 2.6","truncated":false},{"metric":"Comparison","text":"borderline, into PNM (p = 0.069; Kruskal-Wallis test and Dunn's multiple comparisons test)","source":"fulltext","location":"Results 2.6","truncated":false}]},{"id":"pmid-31715362","title":"Nanostructured lipid carriers for oral delivery of silymarin: Improving its absorption and in vivo efficacy in type 2 diabetes and metabolic syndrome model.","year":"2019","journal":"International journal of pharmaceutics","pmid":"31715362","pmcid":null,"doi":"10.1016/j.ijpharm.2019.118838","url":"https://pubmed.ncbi.nlm.nih.gov/31715362/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/31715362/","doiUrl":"https://doi.org/10.1016/j.ijpharm.2019.118838","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation study plus mouse efficacy)","n":null,"formsStudiedRaw":"Milk thistle (silymarin, SLM) in nanostructured lipid carriers (NLCs-CP)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"This study demonstrates the importance of the nanocarriers in increasing the solubility and intestinal permeability of SLM.","source":"fulltext","location":"4. Conclusions","truncated":false},{"metric":"Comparison","text":"The formulation increased the passive permeation of SLM by about 10-fold","source":"fulltext","location":"Results 3.4","truncated":false}]},{"id":"pmid-28553075","title":"Fabrication, characterization and in vitro evaluation of silibinin nanoparticles: an attempt to enhance its oral bioavailability.","year":"2017","journal":"Drug design, development and therapy","pmid":"28553075","pmcid":null,"doi":"10.2147/DDDT.S133806","url":"https://pubmed.ncbi.nlm.nih.gov/28553075/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/28553075/","doiUrl":"https://doi.org/10.2147/DDDT.S133806","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5440029/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation characterization)","n":null,"formsStudiedRaw":"Milk thistle (silibinin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"the NPs of silibinin prepared by the APSP and EPN methods are highly soluble, with a higher dissolution rate compared to that of unprocessed silibinin.","source":"fulltext","location":"Conclusion p.1462","truncated":false},{"metric":"Comparison","text":"solubility of silibinin increases when it is converted to NPs","source":"fulltext","location":"Table 1; Results p.1458","truncated":false},{"metric":"Comparison","text":"the NPs prepared by the EPN method had a better dissolution rate than those prepared by the APSP method","source":"fulltext","location":"Results p.1458","truncated":false}]},{"id":"pmid-26674103","title":"A New Type of Liquid Silymarin Proliposome Containing Bile Salts: Its Preparation and Improved Hepatoprotective Effects.","year":"2015","journal":"PloS one","pmid":"26674103","pmcid":null,"doi":"10.1371/journal.pone.0143625","url":"https://pubmed.ncbi.nlm.nih.gov/26674103/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/26674103/","doiUrl":"https://doi.org/10.1371/journal.pone.0143625","pmcUrl":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4682635/","pdfLink":null,"openAccess":"open access: yes","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro everted gut sac, liposome vs solution)","n":null,"formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"According to the simple everted rat sac transport experiments, silymarin liposome transport across the intestinal barrier is better than for a silymarin solution, which shows that silymarin liposomes are a potential delivery system for silymarin to improve its bioavailability in vivo.","source":"fulltext","location":"Conclusion p.13","truncated":false},{"metric":"Comparison","text":"approximately 1-fold increase in AUC compared to the control group (P<0.01)","source":"fulltext","location":"Results p.8","truncated":false}]},{"id":"pmid-24008629","title":"Binary lipids-based nanostructured lipid carriers for improved oral bioavailability of silymarin.","year":"2014","journal":"Journal of biomaterials applications","pmid":"24008629","pmcid":null,"doi":"10.1177/0885328213485141","url":"https://pubmed.ncbi.nlm.nih.gov/24008629/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/24008629/","doiUrl":"https://doi.org/10.1177/0885328213485141","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"other animal (beagle dog); in vitro also","design":"randomized crossover (three-period crossover)","n":"6","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"It was concluded that nanostructured lipid carriers were potential drug delivery systems to improve the bioavailability of silymarin. Other than improved dissolution, alternative mechanisms such as facilitated absorption as well as lymphatic transport may contribute to bioavailability enhancement.","source":"fulltext","location":"Abstract","truncated":false},{"metric":"Relative bioavailability","text":"2.54-fold that of marketed Legalon capsules","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Relative bioavailability","text":"3.10-fold that of self-made SM-pellets","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"Cmax of SM-NLC was 0.86 ± 0.34 µg/mL, which was significantly higher than 0.22 ± 0.07 of Legalon and 0.25 ± 0.08 of SM-pellets (p < 0.05)","source":"fulltext","location":"Table 2; Results p.893","truncated":false},{"metric":"Comparison","text":"# p<0.05 compared with SM solid dispersion pellets","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"SM-NLC showed even faster absorption although without significant difference (p > 0.05)","source":"fulltext","location":"Results p.893","truncated":false}]},{"id":"pmid-23851081","title":"Silymarin loaded liposomes for hepatic targeting: in vitro evaluation and HepG2 drug uptake.","year":"2013","journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences","pmid":"23851081","pmcid":null,"doi":"10.1016/j.ejps.2013.06.012","url":"https://pubmed.ncbi.nlm.nih.gov/23851081/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/23851081/","doiUrl":"https://doi.org/10.1016/j.ejps.2013.06.012","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation characterization)","n":null,"formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Cellular uptake studies with HepG2 cells demonstrated that Sito-G containing liposomes are potential drug carriers for silymarin to hepatic cells, and that there is an optimum amount of Sito-G needed for maximizing the HepG2 cell uptake of silymarin which was dependent on the liposome composition.","source":"fulltext","location":"Section 4 Conclusion","truncated":false},{"metric":"Comparison","text":"always displayed a higher silymarin uptake with significant differences when compared with the pure silymarin reference solution","source":"fulltext","location":"Results 3.9 p.168","truncated":false},{"metric":"Comparison","text":"and the non-PEGylated liposome (P = 0.0006, 0.0002, 0.0007 and 0.0037, respectively)","source":"fulltext","location":"Results 3.9 p.168","truncated":false},{"metric":"Comparison","text":"with significant differences when compared with the pure silymarin reference solution (12.5 ± 1.0%) (P = 0.0025 and 0.0018, respectively)","source":"fulltext","location":"Results 3.9 p.169","truncated":false},{"metric":"Comparison","text":"and the PEGylated liposome without Sito-G (F6) (P = 0.0011 and 0.0008, respectively)","source":"fulltext","location":"Results 3.9 p.169","truncated":false},{"metric":"Comparison","text":"did not show any significant change in silymarin cellular uptake ... compared to the pure silymarin reference solution (P = 0.0627 and 0.131","source":"fulltext","location":"Results 3.9 p.169","truncated":false},{"metric":"Comparison","text":"they had a significant difference in silymarin cell uptake when compared with the PEGylated liposome without Sito-G (F6) (P = 0.0109 and 0.0107","source":"fulltext","location":"Results 3.9 p.169","truncated":false}]},{"id":"pmid-22343518","title":"Oral bioavailability of silymarin formulated as a novel 3-day delivery system based on porous silica nanoparticles.","year":"2012","journal":"Acta biomaterialia","pmid":"22343518","pmcid":null,"doi":"10.1016/j.actbio.2012.02.011","url":"https://pubmed.ncbi.nlm.nih.gov/22343518/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/22343518/","doiUrl":"https://doi.org/10.1016/j.actbio.2012.02.011","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"other animal (beagle dog); in vitro release also","design":"parallel (4 groups)","n":null,"formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The prepared 3-day release formulation gave an initial burst release from SD, and a sustained release due to the PSNs. The smooth and stable connection of the two actions were attributed to the hydrophilic gel matrix, which showed a considerable increase in bioavailability compared to commercial tablets.","source":"fulltext","location":"Section 4 Conclusion","truncated":false},{"metric":"Cmax","text":"Cmax (490.9 ng ml-1) was reached with Tmax at approximately 1 h","source":"fulltext","location":"Results 3.2 p.2109","truncated":false},{"metric":"AUC","text":"AUC0-∞ of commercial tablets drastically increased from approximately 3.56 µg h ml-1","source":"fulltext","location":"Results 3.2 p.2110","truncated":false},{"metric":"Cmax","text":"Silymarin SD gave the lowest Cmax (236.7 ng ml-1) at approximately 3 h","source":"fulltext","location":"Results 3.2 p.2109","truncated":false},{"metric":"Relative bioavailability","text":"relative bioavailability of silymarin SD was found to be only 29.6%","source":"fulltext","location":"Results 3.2 p.2110","truncated":false},{"metric":"Cmax","text":"Silymarin-loaded PSNs 21.2 241.2 24 22.3 14330.1","source":"fulltext","location":"Table 4","truncated":false},{"metric":"AUC","text":"approximately 3.56 µg h ml-1 to approximately 14.3 and 25.8 µg h ml-1 for drug-loaded PSNs","source":"fulltext","location":"Results 3.2 p.2110","truncated":false},{"metric":"Relative bioavailability","text":"that of silymarin-loaded PSNs was approximately 323.9%","source":"fulltext","location":"Results 3.2 p.2110","truncated":false},{"metric":"Comparison","text":"t1/2 was 54.3 h, approximately 2.43- and 5.72-fold higher than that of silymarin-loaded PSNs and commercial tablets, respectively","source":"fulltext","location":"Results 3.2 p.2110","truncated":false},{"metric":"Comparison","text":"MRT of the 3-day release formulation was 70.2 h, significantly higher than that of silymarin-loaded PSNs and commercial tablets","source":"fulltext","location":"Results 3.2 p.2110","truncated":false}]},{"id":"pmid-22530301","title":"Enhancement of the in-vitro dissolution and in-vivo oral bioavailability of silymarin from liquid-filled hard gelatin capsules of semisolid dispersion using Gelucire 44/14 as a carrier.","year":"2012","journal":"Die Pharmazie","pmid":"22530301","pmcid":null,"doi":null,"url":"https://pubmed.ncbi.nlm.nih.gov/22530301/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/22530301/","doiUrl":null,"pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"other animal (New Zealand albino rabbit); in vitro dissolution also","design":"parallel (3 groups, randomly classified)","n":"18","formsStudiedRaw":"Milk thistle (silymarin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"SD of silymarin with Gelucire 44/14 had a pronounced effect on the drug solubility, in vitro dissolution rates and bioavailability. Further, the relative bioavailability of silymarin SD with Gelucire 44/14 test formulation was superior to that of reference standard (commercial product; Hepaticum).","source":"fulltext","location":"Results/Discussion final paragraph p.212","truncated":false},{"metric":"Cmax","text":"Cmax (µg/ml) 250.62 ± 85.44","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Tmax","text":"Tmax (h) 1.20 ± 0.29","source":"fulltext","location":"Table 2","truncated":false},{"metric":"AUC","text":"AUC0–12 (g.h/ml) 587.53 ± 43.65","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Cmax","text":"1462.10a ± 285.6","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Tmax","text":"Tmax (h) 1.13 ± 0.3","source":"fulltext","location":"Table 2","truncated":false},{"metric":"AUC","text":"4891.7a ± 301","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Cmax","text":"1523.96a ± 350.2","source":"fulltext","location":"Table 2","truncated":false},{"metric":"Comparison","text":"b Significantly different from the commercial product capsule","source":"fulltext","location":"Table 2 footnote b","truncated":false},{"metric":"Comparison","text":"a Significantly different from the silymarin capsules","source":"fulltext","location":"Table 2 footnote a","truncated":false}]},{"id":"pmid-20332565","title":"In vitro and in vivo evaluation of silybin nanosuspensions for oral and intravenous delivery.","year":"2010","journal":"Nanotechnology","pmid":"20332565","pmcid":null,"doi":"10.1088/0957-4484/21/15/155104","url":"https://pubmed.ncbi.nlm.nih.gov/20332565/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/20332565/","doiUrl":"https://doi.org/10.1088/0957-4484/21/15/155104","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"other animal (beagle dog); in vitro Caco-2","design":"other (parallel groups, formulation comparison; oral and IV)","n":"18","formsStudiedRaw":"Milk thistle (silybin)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In accordance with the in vitro drug releasing data and the transport values, the pharmacokinetics study clearly demonstrated that decreasing the particle size of the nanosuspensions could achieve higher oral bioavailability. However, for controlled drug delivery, it is proposed to use the slightly larger particle nanosuspension for IV administration","source":"fulltext","location":"Conclusion p.12-13","truncated":false},{"metric":"Cmax","text":"the nanosuspension dose SN-B (32.7 μg ml−1, 1.335 l kg−1 and 1.674 h, respectively)","source":"fulltext","location":"Discussion (text, PDF p.12)","truncated":false},{"metric":"Cmax","text":"to the solution dose (27.6μg ml−1, 1.443 l kg−1 and 0.733 h, respectively)","source":"fulltext","location":"Discussion (text, PDF p.12)","truncated":false},{"metric":"Comparison","text":"un-milled silybin suspensions showed significantly lower silybin exposure than the nanosuspensions (SN-A and SN-B)","source":"fulltext","location":"Results p.10-11","truncated":false},{"metric":"Comparison","text":"The Cmax was significantly lower in the un-milled silybin suspensions than that of the nanosuspensions SN-A or SN-B","source":"fulltext","location":"Results p.11","truncated":false},{"metric":"Comparison","text":"The tmax was significantly shorter for the un-milled suspension","source":"fulltext","location":"Results p.11","truncated":false},{"metric":"Comparison","text":"statistical difference between the Papp value obtained from the SN-B and all other formulations","source":"fulltext","location":"Results p.10","truncated":false}]},{"id":"pmid-16356669","title":"Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation.","year":"2006","journal":"International journal of pharmaceutics","pmid":"16356669","pmcid":null,"doi":"10.1016/j.ijpharm.2005.11.006","url":"https://pubmed.ncbi.nlm.nih.gov/16356669/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/16356669/","doiUrl":"https://doi.org/10.1016/j.ijpharm.2005.11.006","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"in vitro/ex vivo formulation experiments with 2^3 factorial designs","n":null,"formsStudiedRaw":"Silymarin (buccal liposomal delivery)","formTags":["enhanced"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"In vitro permeation study through chicken cheek pouch of hybrid liposomes containing L:Ch:SA:T 20 of 9:1:1:0.5 molar ratio showed superior permeation results compared with neutral or positively charged liposomes.","source":"fulltext","location":"4. Conclusion","truncated":false},{"metric":"Comparison","text":"The extent of drug permeation after 6 h from products of formulae 1 and 2 was not significantly different relative to that from silymarin suspension (P = 0.072 and 0.131, respectively).","source":"fulltext","location":"Results 3.2","truncated":false},{"metric":"Comparison","text":"(P = 0.072 and 0.131, respectively)","source":"fulltext","location":"Results 3.2","truncated":false},{"metric":"Comparison","text":"Formula 3 produced a significant increase in the permeation of silymarin through chicken pouch (P = 0.013).","source":"fulltext","location":"Results 3.2","truncated":false}]},{"id":"pmid-6870500","title":"[Bioavailability of silymarin, 3: splitting of silybin dihemisuccinate by plasma and liver esterases].","year":"1983","journal":"Archiv der Pharmazie","pmid":"6870500","pmcid":null,"doi":"10.1002/ardp.19833160508","url":"https://pubmed.ncbi.nlm.nih.gov/6870500/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/6870500/","doiUrl":"https://doi.org/10.1002/ardp.19833160508","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro enzyme incubation)","n":null,"formsStudiedRaw":"Milk thistle (silybin dihemisuccinate prodrug / silybin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: complete","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"The conclusion is therefore justified: the succinic acid hemiesters of the silymarin substances fulfil the requirements commonly associated with the term 'prodrug'. (translated from German)","source":"fulltext","location":"p.429, section 'Bedeutung fur die Bioverfugbarkeit'","truncated":false},{"metric":"Comparison","text":"The compound remains unaffected by the plasma esterases, whereas it is totally hydrolysed by the liver esterases within 30 minutes.","source":"fulltext","location":"Abstract; p.428","truncated":false}]},{"id":"pmid-7283681","title":"[Bioavailability of silymarin, I: Volumes of distribution of silybin, silydianin, and silychristin from in-vitro data (author's transl)].","year":"1981","journal":"Archiv der Pharmazie","pmid":"7283681","pmcid":null,"doi":"10.1002/ardp.19813140608","url":"https://pubmed.ncbi.nlm.nih.gov/7283681/","pubmedUrl":"https://pubmed.ncbi.nlm.nih.gov/7283681/","doiUrl":"https://doi.org/10.1002/ardp.19813140608","pmcUrl":null,"pdfLink":null,"openAccess":"open access: no","textUsed":"full text (PDF extraction)","species":"in_vitro","speciesRaw":"in vitro","design":"other (calculation from in-vitro data)","n":null,"formsStudiedRaw":"Milk thistle (silymarin constituents: silybin, silydianin, silychristin)","formTags":["silymarin"],"food":false,"timing":false,"relevance":"full-text extraction: partial","verification":"values extracted verbatim from the full-text PDF (bundle 2, 2026-11-02); reviewer check pending","quotes":[{"metric":"Authors' conclusion","text":"Such calculations based on data obtained in vitro cannot and are not intended to replace in-vivo pharmacokinetic studies (translated from: 'derartige Berechnungen, die auf in vitro gewonnenen Daten beruhen, nicht die Untersuchung der Pharmakokinetik in vivo ersetzen konnen oder sollen').","source":"fulltext","location":"Results/Discussion p.517 last paragraph","truncated":false}]}],"sections":{"forms":{"studyIds":["pmid-40733088","pmid-39204378","pmid-35061161","pmid-30635055","pmid-30108644","pmid-28098838","pmid-26595166","pmid-26642669","pmid-24317417","pmid-23835761","pmid-23072776","pmid-21315924","pmid-21865319","pmid-17913795","pmid-18054294","pmid-18566043","pmid-17077998","pmid-16221754","pmid-16432272","pmid-17315537","pmid-15666173","pmid-12885100","pmid-37695023","pmid-42264004","pmid-42497478","pmid-42956604","pmid-39567122","pmid-39861153","pmid-40493802","pmid-40685047","pmid-37774895","pmid-38529622","pmid-39370820","pmid-39418531","pmid-39498271","pmid-36719351","pmid-36775115","pmid-37457888","pmid-37506470","pmid-37645028","pmid-38093834","pmid-38139990","pmid-35460909","pmid-35560136","pmid-35708053","pmid-35890088","pmid-36178580","pmid-36557984","pmid-33246779","pmid-33257158","pmid-33587330","pmid-33616078","pmid-33925040","pmid-31706011","pmid-31923602","pmid-32337654","pmid-32473632","pmid-30643408","pmid-30668388","pmid-30766782","pmid-30904740","pmid-31185663","pmid-31207432","pmid-31420525","pmid-28503949","pmid-28952834","pmid-28958806","pmid-29162374","pmid-30176941","pmid-30416442","pmid-27436270","pmid-27575878","pmid-28778838","pmid-29026299","pmid-26556526","pmid-25735668","pmid-25848259","pmid-26152876","pmid-26222744","pmid-26543366","pmid-26770331","pmid-24766208","pmid-25149982","pmid-25375210","pmid-24039417","pmid-21802925","pmid-20942611","pmid-21111585","pmid-21549187","pmid-18428992","pmid-19226635","pmid-19470289","pmid-19863195","pmid-18048488","pmid-17328246","pmid-17692492","pmid-16275123","pmid-12748991","pmid-11529693","pmid-9008269","pmid-3398694","pmid-37964172","pmid-39079328","pmid-35300217","pmid-32654568","pmid-26669888","pmid-24495272","pmid-25956049","pmid-21666703","pmid-21948306","pmid-20405254","pmid-20523347","pmid-20621458","pmid-17348898","pmid-16527467","pmid-16687221","pmid-40992023","pmid-41722252","pmid-41729747","pmid-42660255","pmid-38794280","pmid-39344123","pmid-36985575","pmid-37342048","pmid-38144097","pmid-35214124","pmid-34695708","pmid-34944582","pmid-35300372","pmid-33237069","pmid-30448315","pmid-30502425","pmid-30935093","pmid-31052197","pmid-31715362","pmid-28553075","pmid-26674103","pmid-24008629","pmid-23851081","pmid-22343518","pmid-22530301","pmid-20332565","pmid-16356669","pmid-6870500","pmid-7283681"],"evidence":{"grade":"B","basis":"mixed","rationale":"8 human randomized/crossover studies; A-eligible only once the reviewer confirms they agree (capped at B until then). 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Talk to a clinician about what's right for you."}],"evidence_grade":"B","evidence_grade_status":"draft — pending reviewer (rubric v2)","form_grades":{"silymarin":{"label":"Standard silymarin extract","grade":"C","basis":"11 human studies, total n=119, 7 randomized/crossover; median CV 102.85% across 2 matched set(s) (inconsistent)","studies":11,"total_n":119,"randomized":7,"median_cv":102.85,"cv_sets":[{"set":"Cmax / silybin / serum/plasma / fasted / single /  / ng/ml","studies":["30635055","39204378"],"cv":133.4},{"set":"Tmax / silybin / serum/plasma / fasted / single /  / h","studies":["30635055","39204378"],"cv":72.3}],"pmids":["16278402","18566043","19841158","21865319","23835761","26595166","26642669","29273470","30635055","39204378","40733088"]},"phytosome":{"label":"Silybin phytosome (silybin-phosphatidylcholine)","grade":"B","basis":"3 human studies, total n=65, 1 randomized/crossover; median CV 17.0% across 1 matched set(s) (consistent)","studies":3,"total_n":65,"randomized":1,"median_cv":17,"cv_sets":[{"set":"Tmax / silybin / serum/plasma / fasted / single /  / h","studies":["17315537","30635055"],"cv":17}],"pmids":["17315537","18054294","30635055"]},"enhanced":{"label":"Other enhanced formulas (SMEDDS, micellar, water-soluble)","grade":"B","basis":"4 human studies, total n=56, 2 randomized/crossover; consistency not evaluable (no matched set with ≥2 studies)","studies":4,"total_n":56,"randomized":2,"median_cv":null,"cv_sets":[],"pmids":["23072776","30108644","39204378","40733088"]}},"measured_pk":{"slug":"milk-thistle","name":"Milk Thistle (Silymarin)","source":"PDF full-text extraction bundle 2 (1,666 papers), merged 2026-11-02","gradeStatus":"draft — pending reviewer (Dr. Colin Reily)","counts":{"papers":207,"withData":149,"rejected":58,"species":{"rodent":79,"in_vitro":29,"human":25,"other_animal":15,"pig":1},"pkValues":2119},"forms":[{"slug":"silymarin","label":"Standard silymarin extract","n_studies":64,"species":{"rodent":30,"human":18,"other_animal":10,"in_vitro":6},"n_values":964,"pmids":["12885100","15666173","16221754","16278402","16432272","16527467","16687221","17328246","17348898","17913795","18566043","19226635","19470289","19841158","20405254","21111585","21549187","21666703","21865319","21948306","22343518","22530301","23835761","24008629","24039417","24317417","24766208","25149982","25375210","25735668","25848259","25956049","26543366","26595166","26642669","26674103","28098838","28503949","29026299","29273470","30448315","30635055","30904740","31185663","31207432","31420525","32654568","33587330","33616078","33925040","35300217","35708053","35890088","36178580","36557984","36985575","37964172","38529622","39204378","39498271","39567122","40733088","42956604","9008269"]},{"slug":"phytosome","label":"Silybin phytosome (silybin-phosphatidylcholine)","n_studies":7,"species":{"human":3,"rodent":3,"other_animal":1},"n_values":35,"pmids":["17315537","17348898","18054294","25375210","30635055","31207432","39861153"]},{"slug":"enhanced","label":"Other enhanced formulas (SMEDDS, micellar, water-soluble)","n_studies":50,"species":{"rodent":32,"other_animal":10,"human":4,"in_vitro":4},"n_values":313,"pmids":["16527467","16687221","17328246","19863195","20332565","20523347","20621458","21111585","21549187","21666703","23072776","24039417","24495272","25149982","25375210","25956049","26543366","26556526","26669888","26674103","26770331","27436270","27575878","28503949","28778838","29162374","30108644","30448315","30502425","30766782","31207432","31923602","32337654","33246779","33257158","33925040","35300217","35560136","36178580","36719351","37964172","38093834","38139990","39204378","39370820","39418531","39498271","40685047","40733088","42956604"]}],"pairs":[{"grade":"C","basis":"1 human studies (1 randomized/crossover); majority: unclear (0 agree, 0 contradict)","majority":"unclear","tally":{"unclear":1},"pmids":["17348898","30635055","30935093","31207432","35890088"],"anchor":"phytosome-vs-silymarin","a":"phytosome","b":"silymarin","aLabel":"Silybin phytosome (silybin-phosphatidylcholine)","bLabel":"Standard silymarin extract","status":"draft — pending reviewer (Dr. Colin Reily)","rows":[{"pair":"phytosome-vs-silymarin","pmid":"17348898","species":"other_animal","design":"other (parallel design with day-7 switch of test articles in group B; group A silymarin on day 7 after 6-day washout)","n":"16","title":"Bioavailability of a silybin-phosphatidylcholine complex in dogs.","journal":"Journal of veterinary pharmacology and therapeutics","year":"2007","comparison":"SPC (group B) vs silymarin extract groups","parameter":"Cmax and AUC0-24h","direction_text":"SPC > extract","significant":"yes","p_value":"<0.05","direction_DERIVED":"A_better","location":"Table 1","quote":"*P < 0.05 between silymarin extract groups and SPC group."},{"pair":"phytosome-vs-silymarin","pmid":"17348898","species":"other_animal","design":"other (parallel design with day-7 switch of test articles in group B; group A silymarin on day 7 after 6-day washout)","n":"16","title":"Bioavailability of a silybin-phosphatidylcholine complex in dogs.","journal":"Journal of veterinary pharmacology and therapeutics","year":"2007","comparison":"SPC vs silymarin extract","parameter":"Tmax","direction_text":"no significant difference","significant":"no","p_value":"","direction_DERIVED":"no_difference","location":"Results p.134","quote":"There was no statistically significant difference in the Tmax values between the SPC and silymarin extract group of dogs."},{"pair":"phytosome-vs-silymarin","pmid":"17348898","species":"other_animal","design":"other (parallel design with day-7 switch of test articles in group B; group A silymarin on day 7 after 6-day washout)","n":"16","title":"Bioavailability of a silybin-phosphatidylcholine complex in dogs.","journal":"Journal of veterinary pharmacology and therapeutics","year":"2007","comparison":"SPC vs silymarin extract","parameter":"t1/2","direction_text":"very similar","significant":"NR","p_value":"","direction_DERIVED":"no_difference","location":"Results p.134","quote":"The t1/2 for both the SPC and silymarin extract dogs was very similar."},{"pair":"phytosome-vs-silymarin","pmid":"30635055","species":"human","design":"randomized crossover","n":"23 (24 enrolled)","title":"Superior silybin bioavailability of silybin-phosphatidylcholine complex in oily-medium soft-gel capsules versus conventional silymarin tablets in healthy volunteers.","journal":"BMC pharmacology & toxicology","year":"2019","comparison":"A (SPC capsule) vs B (SM tablet)","parameter":"Tmax, Cmax, AUC0-T, AUC0-inf, t1/2","direction_text":"SPC higher Cmax and AUC; shorter Tmax and t1/2","significant":"yes","p_value":"< 0.0001","direction_DERIVED":"unclear","location":"Table 1; Results","quote":"All pharmacokinetic parameters differed significantly between formulations (P < 0.0001)."},{"pair":"phytosome-vs-silymarin","pmid":"30935093","species":"in_vitro","design":"other (in vitro permeability)","n":"NR","title":"Intestinal Permeability Study of Clinically Relevant Formulations of Silibinin in Caco-2 Cell Monolayers.","journal":"International journal of molecular sciences","year":"2019","comparison":"Eurosil85 vs silibinin-PC","parameter":"Papp AP-BL","direction_text":"Eurosil85 > silibinin-PC","significant":"yes","p_value":"<0.0001","direction_DERIVED":"B_better","location":"Fig. 1B legend","quote":"* One-way ANOVA p < 0.0001"},{"pair":"phytosome-vs-silymarin","pmid":"30935093","species":"in_vitro","design":"other (in vitro permeability)","n":"NR","title":"Intestinal Permeability Study of Clinically Relevant Formulations of Silibinin in Caco-2 Cell Monolayers.","journal":"International journal of molecular sciences","year":"2019","comparison":"silibinin-PC vs Eurosil85","parameter":"Papp BL-AP","direction_text":"silibinin-PC > Eurosil85","significant":"yes","p_value":"<0.0001","direction_DERIVED":"A_better","location":"Fig. 1C legend","quote":"* One-way ANOVA p < 0.0001"},{"pair":"phytosome-vs-silymarin","pmid":"30935093","species":"in_vitro","design":"other (in vitro permeability)","n":"NR","title":"Intestinal Permeability Study of Clinically Relevant Formulations of Silibinin in Caco-2 Cell Monolayers.","journal":"International journal of molecular sciences","year":"2019","comparison":"Eurosil85 vs silibinin-PC","parameter":"efflux ratio","direction_text":"Eurosil85 < silibinin-PC","significant":"yes","p_value":"<0.0001","direction_DERIVED":"A_better","location":"Fig. 2A; Results p.3","quote":"was 1.57 (<2), significantly lower than that obtained with silibinin-PC"},{"pair":"phytosome-vs-silymarin","pmid":"30935093","species":"in_vitro","design":"other (in vitro permeability)","n":"NR","title":"Intestinal Permeability Study of Clinically Relevant Formulations of Silibinin in Caco-2 Cell Monolayers.","journal":"International journal of molecular sciences","year":"2019","comparison":"Eurosil85 vs silibinin-PC","parameter":"Pactive","direction_text":"Eurosil85 < silibinin-PC","significant":"yes","p_value":"<0.0001","direction_DERIVED":"A_better","location":"Fig. 2B legend","quote":"* One-way ANOVA p < 0.0001"},{"pair":"phytosome-vs-silymarin","pmid":"31207432","species":"rodent","design":"other (animal formulation comparison; in vitro release, cell assays, hepatoprotection and PK sub-studies)","n":"12 (PK study)","title":"Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats.","journal":"Pharmacological reports : PR","year":"2019","comparison":"L vs S","parameter":"Cmax","direction_text":"conventional liposomes > silymarin suspension (604.48 vs 100.45 ng/ml)","significant":"NR","p_value":"","direction_DERIVED":"unclear","location":"Results p.8 / Table 4","quote":"The Cmax was increased in conventional liposomal formulation administered group to 604.48 ± 14.53 ng/ml without any change in tmax."},{"pair":"phytosome-vs-silymarin","pmid":"31207432","species":"rodent","design":"other (animal formulation comparison; in vitro release, cell assays, hepatoprotection and PK sub-studies)","n":"12 (PK study)","title":"Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats.","journal":"Pharmacological reports : PR","year":"2019","comparison":"L vs S","parameter":"AUC","direction_text":"conventional liposomes > silymarin","significant":"NR","p_value":"","direction_DERIVED":"unclear","location":"Results p.8; Abstract","quote":"The area under the curve (AUC) of the formulation was more than three times higher than silymarin alone"},{"pair":"phytosome-vs-silymarin","pmid":"35890088","species":"rodent","design":"parallel (2 groups, PK)","n":"NR","title":"Phytosomes as a Plausible Nano-Delivery System for Enhanced Oral Bioavailability and Improved Hepatoprotective Activity of Silymarin.","journal":"Pharmaceuticals (Basel, Switzerland)","year":"2022","comparison":"Phytosome (B) vs pure silymarin (A)","parameter":"Cmax, AUC0-t, t1/2, MRT, Cl, Vd","direction_text":"phytosome higher Cmax, AUC0-t, t1/2, MRT; lower Cl and Vd","significant":"yes","p_value":"<0.01","direction_DERIVED":"unclear","location":"Table 5","quote":"optimized silymarin phytosomal formulation showed a significantly higher peak concentration (Cmax = 1.1 ± 0.12 µg/mL) compared to the plain drug"}],"old_grade":"C","grade_v2":"C","grade_v2_basis":"head-to-head and matched single-form evidence agree. H2H: C (1 human studies (1 randomized/crossover); majority: unclear (0 agree, 0 contradict)); indirect: C (2 separated matched set(s), ≥1 studies per form, baseline correction not reported)","indirect_grade":"C"},{"grade":"B","basis":"1 human studies (1 randomized/crossover); majority: first form higher (1 agree, 0 contradict)","majority":"A_better","tally":{"A_better":1},"pmids":["16356669","16687221","20405254","21111585","21549187","21666703","23851081","24039417","25149982","26674103","28503949","31052197","31207432","35300217","36178580","37695023","37964172","39079328","40733088","42497478","42956604"],"anchor":"enhanced-vs-silymarin","a":"enhanced","b":"silymarin","aLabel":"Other enhanced formulas (SMEDDS, micellar, water-soluble)","bLabel":"Standard silymarin extract","status":"draft — pending reviewer (Dr. Colin Reily)","rows":[{"pair":"enhanced-vs-silymarin","pmid":"16356669","species":"in_vitro","design":"in vitro/ex vivo formulation experiments with 2^3 factorial designs","n":"NR","title":"Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation.","journal":"International journal of pharmaceutics","year":"2006","comparison":"F1 vs SUSP","parameter":"permeation extent after 6 h","direction_text":"not significantly different","significant":"no","p_value":"0.072","direction_DERIVED":"no_difference","location":"Results 3.2","quote":"The extent of drug permeation after 6 h from products of formulae 1 and 2 was not significantly different relative to that from silymarin suspension (P = 0.072 and 0.131, respectively)."},{"pair":"enhanced-vs-silymarin","pmid":"16356669","species":"in_vitro","design":"in vitro/ex vivo formulation experiments with 2^3 factorial designs","n":"NR","title":"Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation.","journal":"International journal of pharmaceutics","year":"2006","comparison":"F2 vs SUSP","parameter":"permeation extent after 6 h","direction_text":"not significantly different","significant":"no","p_value":"0.131","direction_DERIVED":"no_difference","location":"Results 3.2","quote":"(P = 0.072 and 0.131, respectively)"},{"pair":"enhanced-vs-silymarin","pmid":"16356669","species":"in_vitro","design":"in vitro/ex vivo formulation experiments with 2^3 factorial designs","n":"NR","title":"Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation.","journal":"International journal of pharmaceutics","year":"2006","comparison":"F3 vs SUSP","parameter":"permeation extent after 6 h","direction_text":"F3 > SUSP","significant":"yes","p_value":"0.013","direction_DERIVED":"A_better","location":"Results 3.2","quote":"Formula 3 produced a significant increase in the permeation of silymarin through chicken pouch (P = 0.013)."},{"pair":"enhanced-vs-silymarin","pmid":"16687221","species":"other_animal","design":"randomized parallel (two groups of 6)","n":"12","title":"Preparation of silymarin proliposome: a new way to increase oral bioavailability of silymarin in beagle dogs.","journal":"International journal of pharmaceutics","year":"2006","comparison":"proliposome vs silymarin capsule","parameter":"Cmax, AUC","direction_text":"proliposome > silymarin (Cmax 472.62 vs 89.78 ng ml-1; AUC0-inf 2606.21 vs 697.04 ng ml-1 h)","significant":"NR","p_value":"","direction_DERIVED":"A_better","location":"Abstract / Tables 2-3","quote":"The high bioavailability of silymarin proliposome could be obtained by oral administration."},{"pair":"enhanced-vs-silymarin","pmid":"20405254","species":"other_animal","design":"randomized crossover","n":"6","title":"Development of silymarin self-microemulsifying drug delivery system with enhanced oral bioavailability.","journal":"AAPS PharmSciTech","year":"2010","comparison":"S (SMEDDS) vs L (Legalon)","parameter":"Cmax","direction_text":"SMEDDS > Legalon","significant":"yes","p_value":"<0.05","direction_DERIVED":"A_better","location":"Results p.677; Table II","quote":"There existed significant difference in Cmax for the two formulations (p<0.05)"},{"pair":"enhanced-vs-silymarin","pmid":"21111585","species":"rodent","design":"parallel (two groups of rats)","n":"8","title":"Oral bioavailability of silymarin phytocomplex formulated as self-emulsifying pellets.","journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology","year":"2011","comparison":"A vs B","parameter":"plasma AUC / relative bioavailability, silybin A","direction_text":"pellets > dry extract (354-fold)","significant":"NR","p_value":"","direction_DERIVED":"unclear","location":"Results p.509","quote":"Bioavailabilities of silybin A and silybin B were 354 and 131 times respectively higher when administered as pellets"},{"pair":"enhanced-vs-silymarin","pmid":"21111585","species":"rodent","design":"parallel (two groups of rats)","n":"8","title":"Oral bioavailability of silymarin phytocomplex formulated as self-emulsifying pellets.","journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology","year":"2011","comparison":"A vs B","parameter":"plasma AUC / relative bioavailability, silybin B","direction_text":"pellets > dry extract (131-fold)","significant":"NR","p_value":"","direction_DERIVED":"unclear","location":"Results p.509","quote":"Bioavailabilities of silybin A and silybin B were 354 and 131 times respectively higher when administered as pellets"},{"pair":"enhanced-vs-silymarin","pmid":"21111585","species":"rodent","design":"parallel (two groups of rats)","n":"8","title":"Oral bioavailability of silymarin phytocomplex formulated as self-emulsifying pellets.","journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology","year":"2011","comparison":"A vs B","parameter":"lymphatic absorption","direction_text":"pellets: silymarin in lymph; dry extract: not quantifiable","significant":"NR","p_value":"","direction_DERIVED":"unclear","location":"Results p.510","quote":"silymarin is absorbed through the lymphatic system when administered as pellets, while it was not present in the lymph at the quantifiable levels when administered as dry extract"},{"pair":"enhanced-vs-silymarin","pmid":"21549187","species":"rodent","design":"parallel (three groups of six rats)","n":"18","title":"Oil based nanocarrier for improved oral delivery of silymarin: In vitro and in vivo studies.","journal":"International journal of pharmaceutics","year":"2011","comparison":"A vs B and A vs C","parameter":"Cmax","direction_text":"TF14 > marketed and bulk drug suspension","significant":"yes","p_value":"<0.01","direction_DERIVED":"unclear","location":"Results p.252","quote":"Cmax of TF14 formulation was significantly higher (p < 0.01) than the marketed conventional formulation and bulk drug suspension"},{"pair":"enhanced-vs-silymarin","pmid":"21549187","species":"rodent","design":"parallel (three groups of six rats)","n":"18","title":"Oil based nanocarrier for improved oral delivery of silymarin: In vitro and in vivo studies.","journal":"International journal of pharmaceutics","year":"2011","comparison":"A vs B and A vs C","parameter":"Tmax","direction_text":"TF14 shorter","significant":"yes","p_value":"<0.01","direction_DERIVED":"unclear","location":"Results p.252","quote":"the difference in tmax of TF14 formulation was significant when compared to tmax of marketed formulation and bulk drug suspension (p < 0.01)"},{"pair":"enhanced-vs-silymarin","pmid":"21666703","species":"other_animal","design":"parallel","n":"6","title":"Proliposomes for oral delivery of dehydrosilymarin: preparation and evaluation in vitro and in vivo.","journal":"Acta pharmacologica Sinica","year":"2011","comparison":"B vs A","parameter":"Cmax","direction_text":"proliposomes > suspension (4.96-fold)","significant":"NR","p_value":"","direction_DERIVED":"A_better","location":"Results p.977","quote":"the Cmax was approximately 4.96-fold higher than that of the dehydrosilymarin suspension"},{"pair":"enhanced-vs-silymarin","pmid":"21666703","species":"other_animal","design":"parallel","n":"6","title":"Proliposomes for oral delivery of dehydrosilymarin: preparation and evaluation in vitro and in vivo.","journal":"Acta pharmacologica Sinica","year":"2011","comparison":"B vs A","parameter":"AUCt","direction_text":"proliposomes > suspension (2.29-fold)","significant":"NR","p_value":"","direction_DERIVED":"A_better","location":"Results p.977","quote":"The AUCt of the vesicle was approximately 2.29-fold higher than that of the dehydrosilymarin suspension"},{"pair":"enhanced-vs-silymarin","pmid":"23851081","species":"in_vitro","design":"other (in vitro formulation characterization)","n":"NR","title":"Silymarin loaded liposomes for hepatic targeting: in vitro evaluation and HepG2 drug uptake.","journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences","year":"2013","comparison":"F2, F3, F4, F5 vs pure silymarin reference: HepG2 uptake","parameter":"cellular uptake","direction_text":"liposomes > reference","significant":"yes","p_value":"0.0003, 0.0002, 0.0003, 0.0008 (F2-F5 vs reference, respectively)","direction_DERIVED":"A_better","location":"Results 3.9 p.168","quote":"always displayed a higher silymarin uptake with significant differences when compared with the pure silymarin reference solution"},{"pair":"enhanced-vs-silymarin","pmid":"23851081","species":"in_vitro","design":"other (in vitro formulation characterization)","n":"NR","title":"Silymarin loaded liposomes for hepatic targeting: in vitro evaluation and HepG2 drug uptake.","journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences","year":"2013","comparison":"F9, F10 vs pure silymarin reference: HepG2 uptake","parameter":"cellular uptake","direction_text":"F9, F10 > reference","significant":"yes","p_value":"0.0025, 0.0018 (F9, F10)","direction_DERIVED":"unclear","location":"Results 3.9 p.169","quote":"with significant differences when compared with the pure silymarin reference solution (12.5 ± 1.0%) (P = 0.0025 and 0.0018, respectively)"},{"pair":"enhanced-vs-silymarin","pmid":"23851081","species":"in_vitro","design":"other (in vitro formulation characterization)","n":"NR","title":"Silymarin loaded liposomes for hepatic targeting: in vitro evaluation and HepG2 drug uptake.","journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences","year":"2013","comparison":"F7, F8 vs pure silymarin reference: HepG2 uptake","parameter":"cellular uptake","direction_text":"no difference","significant":"no","p_value":"0.0627, 0.131 (F7, F8)","direction_DERIVED":"no_difference","location":"Results 3.9 p.169","quote":"did not show any significant change in silymarin cellular uptake ... compared to the pure silymarin reference solution (P = 0.0627 and 0.131"},{"pair":"enhanced-vs-silymarin","pmid":"24039417","species":"rodent","design":"parallel (2 groups)","n":"12 (PK)","title":"Silymarin-loaded solid nanoparticles provide excellent hepatic protection: physicochemical characterization and in vivo evaluation.","journal":"International journal of nanomedicine","year":"2013","comparison":"NP vs COM","parameter":"AUC","direction_text":"NP > COM","significant":"yes","p_value":"<0.05","direction_DERIVED":"A_better","location":"Table 1","quote":"AUC 185.34 ± 25.22* vs 145.18 ± 14.49; *P < 0.05 compared with commercial product"},{"pair":"enhanced-vs-silymarin","pmid":"24039417","species":"rodent","design":"parallel (2 groups)","n":"12 (PK)","title":"Silymarin-loaded solid nanoparticles provide excellent hepatic protection: physicochemical characterization and in vivo evaluation.","journal":"International journal of nanomedicine","year":"2013","comparison":"NP vs COM","parameter":"Cmax","direction_text":"NP > COM","significant":"yes","p_value":"<0.05","direction_DERIVED":"A_better","location":"Table 1","quote":"Cmax 22.07 ± 2.25* vs 15.36 ± 2.25"},{"pair":"enhanced-vs-silymarin","pmid":"24039417","species":"rodent","design":"parallel (2 groups)","n":"12 (PK)","title":"Silymarin-loaded solid nanoparticles provide excellent hepatic protection: physicochemical characterization and in vivo evaluation.","journal":"International journal of nanomedicine","year":"2013","comparison":"NP vs COM","parameter":"Tmax","direction_text":"NP shorter than COM","significant":"yes","p_value":"<0.05","direction_DERIVED":"unclear","location":"Table 1","quote":"the time taken to reach peak drug levels for the nanoparticles was significantly shorter"},{"pair":"enhanced-vs-silymarin","pmid":"24039417","species":"rodent","design":"parallel (2 groups)","n":"12 (PK)","title":"Silymarin-loaded solid nanoparticles provide excellent hepatic protection: physicochemical characterization and in vivo evaluation.","journal":"International journal of nanomedicine","year":"2013","comparison":"NP vs COM","parameter":"t1/2 and Kel","direction_text":"no considerable difference","significant":"no","p_value":"","direction_DERIVED":"no_difference","location":"Results p.3341","quote":"the Kel and t1/2 values of the drug did not vary considerably between these two groups"},{"pair":"enhanced-vs-silymarin","pmid":"24039417","species":"rodent","design":"parallel (2 groups)","n":"12 (PK)","title":"Silymarin-loaded solid nanoparticles provide excellent hepatic protection: physicochemical characterization and in vivo evaluation.","journal":"International journal of nanomedicine","year":"2013","comparison":"NP vs COM","parameter":"initial plasma concentrations 0.25 and 1.5 h","direction_text":"NP > COM","significant":"yes","p_value":"<0.05","direction_DERIVED":"A_better","location":"Results p.3341; Fig. 6","quote":"initial plasma concentrations of drugs in nanoparticles between 0.25 and 1.5 hours were impressively higher than those in the commercial product (P < 0.05)"},{"pair":"enhanced-vs-silymarin","pmid":"25149982","species":"rodent","design":"parallel (2 groups)","n":"12","title":"Silymarin liposomes improves oral bioavailability of silybin besides targeting hepatocytes, and immune cells.","journal":"Pharmacological reports : PR","year":"2014","comparison":"LIP vs SIL","parameter":"AUC0-2 and Cmax","direction_text":"LIP > SIL","significant":"NR","p_value":"","direction_DERIVED":"A_better","location":"Table 4; Results p.796","quote":"Cmax was increased by liposomal formulation to 716.40 ± 42.85 ng/ml without a change in tmax"},{"pair":"enhanced-vs-silymarin","pmid":"25149982","species":"rodent","design":"parallel (2 groups)","n":"12","title":"Silymarin liposomes improves oral bioavailability of silybin besides targeting hepatocytes, and immune cells.","journal":"Pharmacological reports : PR","year":"2014","comparison":"LIP vs SIL","parameter":"half-life","direction_text":"LIP shorter (0.67 vs 1.28 h)","significant":"NR","p_value":"","direction_DERIVED":"unclear","location":"Table 4; Discussion","quote":"Decrease in half-life and increase elimination rate constant can be justified by selective clearance of liposome by Kupffer cells."},{"pair":"enhanced-vs-silymarin","pmid":"26674103","species":"in_vitro","design":"other (in vitro everted gut sac, liposome vs solution)","n":"NR","title":"A New Type of Liquid Silymarin Proliposome Containing Bile Salts: Its Preparation and Improved Hepatoprotective Effects.","journal":"PloS one","year":"2015","comparison":"A (liposome) vs B (control solution)","parameter":"AUC of serosal absorption","direction_text":"liposome > control solution","significant":"yes","p_value":"<0.01","direction_DERIVED":"A_better","location":"Results p.8","quote":"approximately 1-fold increase in AUC compared to the control group (P<0.01)"},{"pair":"enhanced-vs-silymarin","pmid":"28503949","species":"rodent","design":"parallel","n":"NR","title":"Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization.","journal":"Artificial cells, nanomedicine, and biotechnology","year":"2018","comparison":"C (NE9) vs A (standard suspension)","parameter":"Cmax","direction_text":"NE9 > standard","significant":"yes","p_value":"<.01","direction_DERIVED":"unclear","location":"Table 4; Results p.237","quote":"The Cmax of NE9 was found to be 38.62 ± 2.43 µg/ml. That was higher than silymarin-marketed suspension (10.36 ± 1.06) and standard suspension (5.24 ± 4.31)"},{"pair":"enhanced-vs-silymarin","pmid":"28503949","species":"rodent","design":"parallel","n":"NR","title":"Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization.","journal":"Artificial cells, nanomedicine, and biotechnology","year":"2018","comparison":"C vs B (conventional suspension)","parameter":"Cmax","direction_text":"NE9 > conventional","significant":"yes","p_value":"<.05","direction_DERIVED":"unclear","location":"Table 4","quote":""},{"pair":"enhanced-vs-silymarin","pmid":"28503949","species":"rodent","design":"parallel","n":"NR","title":"Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization.","journal":"Artificial cells, nanomedicine, and biotechnology","year":"2018","comparison":"C vs A","parameter":"AUC0-all","direction_text":"NE9 > standard","significant":"yes","p_value":"<.01","direction_DERIVED":"unclear","location":"Table 4; Results p.238","quote":"17-fold higher than standard suspension (17.82 ± 7.32) (p < .01)"},{"pair":"enhanced-vs-silymarin","pmid":"28503949","species":"rodent","design":"parallel","n":"NR","title":"Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization.","journal":"Artificial cells, nanomedicine, and biotechnology","year":"2018","comparison":"C vs B","parameter":"AUC0-all","direction_text":"NE9 > conventional","significant":"yes","p_value":"<.01","direction_DERIVED":"unclear","location":"Table 4","quote":"8-fold higher than marketed suspension"},{"pair":"enhanced-vs-silymarin","pmid":"28503949","species":"rodent","design":"parallel","n":"NR","title":"Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization.","journal":"Artificial cells, nanomedicine, and biotechnology","year":"2018","comparison":"C vs A and B","parameter":"Tmax","direction_text":"NE9 shorter","significant":"yes","p_value":"<.01 vs standard; <.05 vs conventional","direction_DERIVED":"unclear","location":"Table 4","quote":"shorter Tmax (p < .05) compared with conventional and standard suspensions of silymarin (Abstract)"},{"pair":"enhanced-vs-silymarin","pmid":"31052197","species":"in_vitro","design":"other (in vitro formulation characterization)","n":"NR","title":"Formulation of Nanomicelles to Improve the Solubility and the Oral Absorption of Silymarin.","journal":"Molecules (Basel, Switzerland)","year":"2019","comparison":"SLM-MNM vs free-SLM","parameter":"PAMPA Pe","direction_text":"SLM-MNM > free-SLM","significant":"yes","p_value":"<0.01","direction_DERIVED":"A_better","location":"Fig. 4; Results 2.6","quote":"** p < 0.01 vs. free-SLM"},{"pair":"enhanced-vs-silymarin","pmid":"31052197","species":"in_vitro","design":"other (in vitro formulation characterization)","n":"NR","title":"Formulation of Nanomicelles to Improve the Solubility and the Oral Absorption of Silymarin.","journal":"Molecules (Basel, Switzerland)","year":"2019","comparison":"SLM-PNM vs free-SLM","parameter":"PAMPA Pe","direction_text":"SLM-PNM > free-SLM (borderline)","significant":"no","p_value":"0.069","direction_DERIVED":"no_difference","location":"Results 2.6","quote":"borderline, into PNM (p = 0.069; Kruskal-Wallis test and Dunn's multiple comparisons test)"},{"pair":"enhanced-vs-silymarin","pmid":"31207432","species":"rodent","design":"other (animal formulation comparison; in vitro release, cell assays, hepatoprotection and PK sub-studies)","n":"12 (PK study)","title":"Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats.","journal":"Pharmacological reports : PR","year":"2019","comparison":"L vs S","parameter":"Cmax","direction_text":"conventional liposomes > silymarin suspension (604.48 vs 100.45 ng/ml)","significant":"NR","p_value":"","direction_DERIVED":"A_better","location":"Results p.8 / Table 4","quote":"The Cmax was increased in conventional liposomal formulation administered group to 604.48 ± 14.53 ng/ml without any change in tmax."},{"pair":"enhanced-vs-silymarin","pmid":"31207432","species":"rodent","design":"other (animal formulation comparison; in vitro release, cell assays, hepatoprotection and PK sub-studies)","n":"12 (PK study)","title":"Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats.","journal":"Pharmacological reports : PR","year":"2019","comparison":"L vs S","parameter":"AUC","direction_text":"conventional liposomes > silymarin","significant":"NR","p_value":"","direction_DERIVED":"A_better","location":"Results p.8; Abstract","quote":"The area under the curve (AUC) of the formulation was more than three times higher than silymarin alone"},{"pair":"enhanced-vs-silymarin","pmid":"35300217","species":"other_animal","design":"parallel (randomized two groups) plus in vitro dissolution","n":"16","title":"In vitro Dissolution Testing and Pharmacokinetic Studies of Silymarin Solid Dispersion After Oral Administration to Healthy Pigs.","journal":"Frontiers in veterinary science","year":"2022","comparison":"SD vs PM","parameter":"Cmax","direction_text":"SD higher (1,190.02 vs 411.35 ng ml−1)","significant":"yes","p_value":"<0.05","direction_DERIVED":"unclear","location":"Table 4","quote":"The Cmax and AUC0−∞ for the solid dispersion group were both statistically different (p < 0.05) from the premix group."},{"pair":"enhanced-vs-silymarin","pmid":"35300217","species":"other_animal","design":"parallel (randomized two groups) plus in vitro dissolution","n":"16","title":"In vitro Dissolution Testing and Pharmacokinetic Studies of Silymarin Solid Dispersion After Oral Administration to Healthy Pigs.","journal":"Frontiers in veterinary science","year":"2022","comparison":"SD vs PM","parameter":"AUC0-∞","direction_text":"SD higher (1,299.19 vs 586.82 ng ml−1 h)","significant":"yes","p_value":"<0.05","direction_DERIVED":"unclear","location":"Table 4","quote":"The Cmax and AUC0−∞ for the solid dispersion group were both statistically different (p < 0.05)"},{"pair":"enhanced-vs-silymarin","pmid":"35300217","species":"other_animal","design":"parallel (randomized two groups) plus in vitro dissolution","n":"16","title":"In vitro Dissolution Testing and Pharmacokinetic Studies of Silymarin Solid Dispersion After Oral Administration to Healthy Pigs.","journal":"Frontiers in veterinary science","year":"2022","comparison":"SD vs PM","parameter":"Vd","direction_text":"SD lower (112.10 vs 239.34 L kg−1)","significant":"yes","p_value":"<0.05","direction_DERIVED":"unclear","location":"Table 4","quote":""},{"pair":"enhanced-vs-silymarin","pmid":"35300217","species":"other_animal","design":"parallel (randomized two groups) plus in vitro dissolution","n":"16","title":"In vitro Dissolution Testing and Pharmacokinetic Studies of Silymarin Solid Dispersion After Oral Administration to Healthy Pigs.","journal":"Frontiers in veterinary science","year":"2022","comparison":"SD vs PM","parameter":"Kel, t1/2, Tmax, MRT","direction_text":"no difference","significant":"no","p_value":">0.05","direction_DERIVED":"no_difference","location":"Table 4","quote":"no significant statistical difference was observed for pharmacokinetic parameters ... such as Kel, t1/2, and Tmax"},{"pair":"enhanced-vs-silymarin","pmid":"35300217","species":"other_animal","design":"parallel (randomized two groups) plus in vitro dissolution","n":"16","title":"In vitro Dissolution Testing and Pharmacokinetic Studies of Silymarin Solid Dispersion After Oral Administration to Healthy Pigs.","journal":"Frontiers in veterinary science","year":"2022","comparison":"SD vs PM","parameter":"relative bioavailability (stated ratios)","direction_text":"Cmax about x2.9, AUC about x2.2 that of premix; text also says peak '~3-fold greater' and 'relative bioavailability increased more than 2-fold (Table 4)'","significant":"NR","p_value":"","direction_DERIVED":"unclear","location":"Results p.3; Discussion p.5","quote":"Cmax and AUC in pharmacokinetics were about ×2.9 and ×2.2 that of the premix group"},{"pair":"enhanced-vs-silymarin","pmid":"35300217","species":"other_animal","design":"parallel (randomized two groups) plus in vitro dissolution","n":"16","title":"In vitro Dissolution Testing and Pharmacokinetic Studies of Silymarin Solid Dispersion After Oral Administration to Healthy Pigs.","journal":"Frontiers in veterinary science","year":"2022","comparison":"SD vs PM","parameter":"in vitro cumulative release","direction_text":"SD about 2.5-fold higher than premix (total released per unit time)","significant":"NR","p_value":"","direction_DERIVED":"unclear","location":"Results p.3","quote":"the total released per unit time was 2.5-fold higher (Table 2, Figure 1)"},{"pair":"enhanced-vs-silymarin","pmid":"36178580","species":"rodent","design":"parallel (3 groups per experiment), two separate experiments","n":"NR","title":"Enhanced bioavailability and hepatoprotective effect of silymarin by preparing silymarin-loaded solid dispersion formulation using freeze-drying method.","journal":"Archives of pharmacal research","year":"2022","comparison":"E2-C vs E2-A and E2-B","parameter":"Cmax, AUC8h, AUC∞","direction_text":"SD > PM > silymarin","significant":"yes","p_value":"<0.05","direction_DERIVED":"unclear","location":"Table 2","quote":"the relative BA increased to 589% compared with the silymarin group"},{"pair":"enhanced-vs-silymarin","pmid":"37695023","species":"pig","design":"parallel","n":"18 (Experiment 2)","title":"Supplemental impact of silymarin in growing pig diet on the growth performance, total tract digestibility, faecal microflora, faecal noxious gas emission and absorption rate in blood.","journal":"Journal of animal physiology and animal nutrition","year":"2024","comparison":"Micelle-type (TRT4-6) vs powdered (TRT1-3) silymarin, plasma concentration at 1 h","parameter":"plasma silymarin (ng/mL)","direction_text":"micelle > powder","significant":"yes","p_value":"0.0018","direction_DERIVED":"A_better","location":"Table 6","quote":"micelle-type silymarin showed higher (p < 0.05) absorption rate compared to the powdered type silymarin in 1st, 2nd, 4th, 8th, 12th and 24th h"},{"pair":"enhanced-vs-silymarin","pmid":"37695023","species":"pig","design":"parallel","n":"18 (Experiment 2)","title":"Supplemental impact of silymarin in growing pig diet on the growth performance, total tract digestibility, faecal microflora, faecal noxious gas emission and absorption rate in blood.","journal":"Journal of animal physiology and animal nutrition","year":"2024","comparison":"TRT4-6 vs TRT1-3 at 2 h","parameter":"plasma silymarin (ng/mL)","direction_text":"micelle > powder","significant":"yes","p_value":"0.0053","direction_DERIVED":"A_better","location":"Table 6","quote":""},{"pair":"enhanced-vs-silymarin","pmid":"37695023","species":"pig","design":"parallel","n":"18 (Experiment 2)","title":"Supplemental impact of silymarin in growing pig diet on the growth performance, total tract digestibility, faecal microflora, faecal noxious gas emission and absorption rate in blood.","journal":"Journal of animal physiology and animal nutrition","year":"2024","comparison":"TRT4-6 vs TRT1-3 at 4 h","parameter":"plasma silymarin (ng/mL)","direction_text":"micelle > powder","significant":"yes","p_value":"0.0312","direction_DERIVED":"A_better","location":"Table 6","quote":""},{"pair":"enhanced-vs-silymarin","pmid":"37695023","species":"pig","design":"parallel","n":"18 (Experiment 2)","title":"Supplemental impact of silymarin in growing pig diet on the growth performance, total tract digestibility, faecal microflora, faecal noxious gas emission and absorption rate in blood.","journal":"Journal of animal physiology and animal nutrition","year":"2024","comparison":"TRT4-6 vs TRT1-3 at 8 h","parameter":"plasma silymarin (ng/mL)","direction_text":"micelle > powder","significant":"yes","p_value":"0.0118","direction_DERIVED":"A_better","location":"Table 6","quote":""},{"pair":"enhanced-vs-silymarin","pmid":"37695023","species":"pig","design":"parallel","n":"18 (Experiment 2)","title":"Supplemental impact of silymarin in growing pig diet on the growth performance, total tract digestibility, faecal microflora, faecal noxious gas emission and absorption rate in blood.","journal":"Journal of animal physiology and animal nutrition","year":"2024","comparison":"TRT4-6 vs TRT1-3 at 12 h","parameter":"plasma silymarin (ng/mL)","direction_text":"micelle > powder","significant":"yes","p_value":"0.0073","direction_DERIVED":"A_better","location":"Table 6","quote":""},{"pair":"enhanced-vs-silymarin","pmid":"37695023","species":"pig","design":"parallel","n":"18 (Experiment 2)","title":"Supplemental impact of silymarin in growing pig diet on the growth performance, total tract digestibility, faecal microflora, faecal noxious gas emission and absorption rate in blood.","journal":"Journal of animal physiology and animal nutrition","year":"2024","comparison":"TRT4-6 vs TRT1-3 at 24 h","parameter":"plasma silymarin (ng/mL)","direction_text":"micelle > powder","significant":"yes","p_value":"0.0010","direction_DERIVED":"A_better","location":"Table 6","quote":""},{"pair":"enhanced-vs-silymarin","pmid":"37964172","species":"other_animal","design":"randomized crossover","n":"6","title":"A comparative study on the preparation and evaluation of solubilizing systems for silymarin.","journal":"Drug delivery and translational research","year":"2024","comparison":"SM-SMEDDS vs SM and vs Legalon®, SB Cmax","parameter":"Cmax","direction_text":"SM-SMEDDS > SM, SM-SMEDDS > Legalon®","significant":"yes","p_value":"<0.05","direction_DERIVED":"A_better","location":"Results 3.5.2; Table 3","quote":"SM-SMEDDS exhibited a significantly improved Cmax compared to both SM (p < 0.05) and Legalon® (p < 0.05)"},{"pair":"enhanced-vs-silymarin","pmid":"37964172","species":"other_animal","design":"randomized crossover","n":"6","title":"A comparative study on the preparation and evaluation of solubilizing systems for silymarin.","journal":"Drug delivery and translational research","year":"2024","comparison":"SM-SMEDDS vs Legalon®, SB relative bioavailability (AUC)","parameter":"AUC0-t / relative bioavailability","direction_text":"SM-SMEDDS > Legalon®","significant":"yes","p_value":"<0.05","direction_DERIVED":"A_better","location":"Results 3.5.2","quote":"SM-SMEDDS can dramatically enhanced the bioavailability of SM, even compared to Legalon® (p < 0.05)"},{"pair":"enhanced-vs-silymarin","pmid":"39079328","species":"other_animal","design":"parallel (two dietary groups), Experiment 2; Experiment 1 was a 3-group dose-response feeding trial","n":"192 hens (Experiment 2); 288 hens (Experiment 1)","title":"Effects of micelle silymarin in corn-soybean meal-based diet on laying hens' performance, egg quality, and blood profile, with comparative assessment of blood absorption rates between powdered and micelle silymarin.","journal":"Poultry science","year":"2024","comparison":"Micelle silymarin (TRT2) vs powder silymarin (TRT1)","parameter":"blood silymarin 'absorption rate' at 2 h","direction_text":"TRT2 > TRT1","significant":"yes","p_value":"0.0322","direction_DERIVED":"unclear","location":"Table 5","quote":"micelletype silymarin showed a higher (p < 0.05) absorption rate compared to the powdered-type silymarin in 2nd, 4th h."},{"pair":"enhanced-vs-silymarin","pmid":"39079328","species":"other_animal","design":"parallel (two dietary groups), Experiment 2; Experiment 1 was a 3-group dose-response feeding trial","n":"192 hens (Experiment 2); 288 hens (Experiment 1)","title":"Effects of micelle silymarin in corn-soybean meal-based diet on laying hens' performance, egg quality, and blood profile, with comparative assessment of blood absorption rates between powdered and micelle silymarin.","journal":"Poultry science","year":"2024","comparison":"Micelle silymarin (TRT2) vs powder silymarin (TRT1)","parameter":"blood silymarin 'absorption rate' at 4 h","direction_text":"TRT2 > TRT1","significant":"yes","p_value":"0.0483","direction_DERIVED":"unclear","location":"Table 5","quote":"micelletype silymarin showed a higher (p < 0.05) absorption rate compared to the powdered-type silymarin in 2nd, 4th h."},{"pair":"enhanced-vs-silymarin","pmid":"40733088","species":"human","design":"randomized crossover (double-blind)","n":"16","title":"Novel Micellar Formulation of Silymarin (Milk Thistle) with Enhanced Bioavailability in a Double-Blind, Randomized, Crossover Human Trial.","journal":"Pharmaceutics","year":"2025","comparison":"LMM vs STD","parameter":"Cmax","direction_text":"LMM > STD","significant":"yes","p_value":"0.035 (Table 3); 0.007 (abstract)","direction_DERIVED":"A_better","location":"Table 3; Abstract","quote":"18.9-fold higher Cmax"},{"pair":"enhanced-vs-silymarin","pmid":"40733088","species":"human","design":"randomized crossover (double-blind)","n":"16","title":"Novel Micellar Formulation of Silymarin (Milk Thistle) with Enhanced Bioavailability in a Double-Blind, Randomized, Crossover Human Trial.","journal":"Pharmaceutics","year":"2025","comparison":"LMM vs STD","parameter":"AUC0-24h","direction_text":"LMM > STD","significant":"yes","p_value":"0.046 (Table 3); 0.015 (abstract, Results text)","direction_DERIVED":"A_better","location":"Table 3; Abstract; Results 3.2","quote":"11.4-fold higher AUC0–24"},{"pair":"enhanced-vs-silymarin","pmid":"40733088","species":"human","design":"randomized crossover (double-blind)","n":"16","title":"Novel Micellar Formulation of Silymarin (Milk Thistle) with Enhanced Bioavailability in a Double-Blind, Randomized, Crossover Human Trial.","journal":"Pharmaceutics","year":"2025","comparison":"LMM vs STD","parameter":"Tmax","direction_text":"LMM shorter than STD","significant":"yes","p_value":"0.035 (Table 3); 0.015 (abstract, Results text)","direction_DERIVED":"unclear","location":"Table 3; Abstract","quote":"Tmax was 0.5 ... hours for the micellar formulation versus 2.5"},{"pair":"enhanced-vs-silymarin","pmid":"40733088","species":"human","design":"randomized crossover (double-blind)","n":"16","title":"Novel Micellar Formulation of Silymarin (Milk Thistle) with Enhanced Bioavailability in a Double-Blind, Randomized, Crossover Human Trial.","journal":"Pharmaceutics","year":"2025","comparison":"LMM vs STD","parameter":"MRT","direction_text":"STD > LMM","significant":"yes","p_value":"0.046 (Table 3); 0.015 (abstract, Results text)","direction_DERIVED":"B_better","location":"Table 3; Abstract","quote":"standard formulation exhibited a significantly longer mean residence time"},{"pair":"enhanced-vs-silymarin","pmid":"40733088","species":"human","design":"randomized crossover (double-blind)","n":"16","title":"Novel Micellar Formulation of Silymarin (Milk Thistle) with Enhanced Bioavailability in a Double-Blind, Randomized, Crossover Human Trial.","journal":"Pharmaceutics","year":"2025","comparison":"LMM vs STD","parameter":"T1/2","direction_text":"no difference","significant":"no","p_value":"0.195","direction_DERIVED":"no_difference","location":"Table 3; Results 3.2","quote":"the T½ levels were not significantly different between the standard formulation and LMM"},{"pair":"enhanced-vs-silymarin","pmid":"42497478","species":"rodent","design":"other (formulation comparison, free vs nanoparticle)","n":"NR","title":"Silica-installed redox nanoparticles enable effective oral silymarin therapy for liver fibrosis.","journal":"Colloids and surfaces. B, Biointerfaces","year":"2026","comparison":"B vs A","parameter":"hepatic silymarin accumulation (0.5, 1 h)","direction_text":"Sil@siRNP > free silymarin","significant":"yes","p_value":"**p<0.01, ***p<0.001 (legend; which time points NR)","direction_DERIVED":"unclear","location":"Results 3.2 / Fig. 2F","quote":"oral administration of Sil@siRNP significantly increased hepatic accumulation of silymarin compared with free silymarin"},{"pair":"enhanced-vs-silymarin","pmid":"42956604","species":"rodent","design":"parallel (4 groups)","n":"24 (4 groups x 6, as stated)","title":"Microencapsulated silymarin nanoparticles prepared by atomized instantaneous solidification: Structural characterization, molecular interactions, improved solubility and bioavailability.","journal":"Food chemistry","year":"2026","comparison":"A vs B vs C","parameter":"Cmax","direction_text":"C > B > A (different letters a, b, c)","significant":"yes","p_value":"<0.05","direction_DERIVED":"unclear","location":"Table 2","quote":"Significant differences (P < 0.05) are indicated with different letters."},{"pair":"enhanced-vs-silymarin","pmid":"42956604","species":"rodent","design":"parallel (4 groups)","n":"24 (4 groups x 6, as stated)","title":"Microencapsulated silymarin nanoparticles prepared by atomized instantaneous solidification: Structural characterization, molecular interactions, improved solubility and bioavailability.","journal":"Food chemistry","year":"2026","comparison":"A vs B vs C","parameter":"AUC0-t, AUC0-inf","direction_text":"B and C > A; B and C not different (both letter a)","significant":"yes","p_value":"<0.05","direction_DERIVED":"unclear","location":"Table 2","quote":"Significant differences (P < 0.05) are indicated with different letters."},{"pair":"enhanced-vs-silymarin","pmid":"42956604","species":"rodent","design":"parallel (4 groups)","n":"24 (4 groups x 6, as stated)","title":"Microencapsulated silymarin nanoparticles prepared by atomized instantaneous solidification: Structural characterization, molecular interactions, improved solubility and bioavailability.","journal":"Food chemistry","year":"2026","comparison":"A vs B vs C","parameter":"Tmax","direction_text":"A later than B and C","significant":"yes","p_value":"<0.05","direction_DERIVED":"unclear","location":"Table 2","quote":""}],"old_grade":"B","grade_v2":"B","grade_v2_basis":"head-to-head only; no matched single-form separation. H2H: B (1 human studies (1 randomized/crossover); majority: first form higher (1 agree, 0 contradict)); indirect: none","indirect_grade":null}],"pk":[{"pmid":"12885100","species":"human","arm":"","form":"Indinavir (Crixivan) (Merck & Co.)","forms":[],"dose":"800 mg","doseBasis":"NR","fed":"fasted","n":"10","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"AUC","detail":"AUC0-8 steady state","value":"20.7","variance":"","units":"hr•mg/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"12885100","species":"human","arm":"","form":"Indinavir (Crixivan) (Merck & Co.)","forms":[],"dose":"800 mg","doseBasis":"NR","fed":"fasted","n":"10","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"Cmax","detail":"","value":"8.85","variance":"","units":"mg/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"12885100","species":"human","arm":"","form":"Indinavir (Crixivan) plus standardized milk thistle (silymarin 160 mg capsules; assayed 173 mg/capsule) (General Nutrition Corp. (milk thistle))","forms":["silymarin"],"dose":"800 (indinavir); 160 (silymarin) mg","doseBasis":"NR","fed":"fasted","n":"10","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"AUC","detail":"AUC0-8 steady state","value":"19.4","variance":"","units":"hr•mg/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"12885100","species":"human","arm":"","form":"Indinavir (Crixivan) plus standardized milk thistle (silymarin 160 mg capsules; assayed 173 mg/capsule) (General Nutrition Corp. (milk thistle))","forms":["silymarin"],"dose":"800 (indinavir); 160 (silymarin) mg","doseBasis":"NR","fed":"fasted","n":"10","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"Cmax","detail":"","value":"7.85","variance":"","units":"mg/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"12885100","species":"human","arm":"","form":"Indinavir (Crixivan) (Merck & Co.)","forms":[],"dose":"800 mg","doseBasis":"NR","fed":"fasted","n":"10","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"AUC","detail":"AUC0-8, text (Abstract)","value":"20.7","variance":"","units":"hr•mg/L","location":"Abstract","quote":"","quoteCheck":"no quote","note":""},{"pmid":"12885100","species":"human","arm":"","form":"Indinavir (Crixivan) plus standardized milk thistle (silymarin 160 mg capsules; assayed 173 mg/capsule) (General Nutrition Corp. (milk thistle))","forms":["silymarin"],"dose":"800 (indinavir); 160 (silymarin) mg","doseBasis":"NR","fed":"fasted","n":"10","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"AUC","detail":"AUC0-8, text (Abstract)","value":"19.4","variance":"","units":"hr•mg/L","location":"Abstract","quote":"","quoteCheck":"no quote","note":""},{"pmid":"12885100","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"AUC","detail":"difference in geometric mean AUC0-8, indinavir alone vs with silymarin","value":"1.38","variance":"","units":"hr•mg/L","location":"Results p.3","quote":"1.38 hr•mg/L [0.79-1.48 hr•mg/L]) was not significant (p=0.64)","quoteCheck":"supported","note":"Printed as 'difference [95% CI]' of geometric means"},{"pmid":"12885100","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"Cmax","detail":"difference in geometric mean Cmax, indinavir alone vs with silymarin","value":"1.0","variance":"","units":"mg/L","location":"Results p.3","quote":"The geometric mean [95% CI] difference in Cmax (1.0 mg/L [0.88-1.4 mg/L]) also was not significant (p=0.30)","quoteCheck":"supported","note":""},{"pmid":"12885100","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"relative_bioavailability","detail":"AUC0-8 geometric mean ratio (indinavir + silymarin vs alone); did not meet 0.80-1.25 bioequivalence","value":"0.93","variance":"","units":"hr•mg/L","location":"Results p.3","quote":"geometric mean ratio [90% CI] of indinavir AUC 0-8 (0.93 hr•mg/L [0.72-1.2 hr•mg/L])","quoteCheck":"supported","note":"Ratio printed with units hr•mg/L in the paper"},{"pmid":"12885100","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Cmax geometric mean ratio (indinavir + silymarin vs alone); did not meet 0.80-1.25 bioequivalence","value":"0.89","variance":"","units":"mg/L","location":"Results p.3","quote":"geometric mean ratio [90% CI] of indinavir Cmax (0.89 mg/L [0.72-1.1 mg/L])","quoteCheck":"supported","note":"Ratio printed with units mg/L in the paper"},{"pmid":"15666173","species":"human","arm":"","form":"Milk thistle extract tablets/capsules (456 mg silymarins per tablet; abstract says 450 mg capsules) plus indinavir 800 mg (Kare and Hope Ltd/Inc., Toronto (milk thistle); Merck Frosst (indinavir))","forms":["silymarin"],"dose":"456 mg silymarins per tablet, one tablet three times per day (indinavir 800 mg every 8 h)","doseBasis":"NR","fed":"fasting for indinavir PK days","n":"8","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"Cmax","detail":"Cmax","value":"9.76","variance":"","units":"µg/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 headed 'Geometric mean indinavir pharmacokinetic parameters'"},{"pmid":"15666173","species":"human","arm":"","form":"Milk thistle extract tablets/capsules (456 mg silymarins per tablet; abstract says 450 mg capsules) plus indinavir 800 mg (Kare and Hope Ltd/Inc., Toronto (milk thistle); Merck Frosst (indinavir))","forms":["silymarin"],"dose":"456 mg silymarins per tablet, one tablet three times per day (indinavir 800 mg every 8 h)","doseBasis":"NR","fed":"fasting for indinavir PK days","n":"8","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"AUC","detail":"AUC0-8","value":"22.7","variance":"","units":"h µg/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 headed 'Geometric mean indinavir pharmacokinetic parameters'"},{"pmid":"15666173","species":"human","arm":"","form":"Indinavir 800 mg every 8 h; no plant extract (Merck Frosst)","forms":[],"dose":"800 mg indinavir every 8 h","doseBasis":"NR","fed":"fasting","n":"8","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"Cmax","detail":"Cmax","value":"9.96","variance":"","units":"µg/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 headed 'Geometric mean indinavir pharmacokinetic parameters'"},{"pmid":"15666173","species":"human","arm":"","form":"Indinavir 800 mg every 8 h; no plant extract (Merck Frosst)","forms":[],"dose":"800 mg indinavir every 8 h","doseBasis":"NR","fed":"fasting","n":"8","analyte":"indinavir (not the listed supplement)","matrix":"plasma","parameter":"AUC","detail":"AUC0-8","value":"24.3","variance":"","units":"h µg/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 headed 'Geometric mean indinavir pharmacokinetic parameters'"},{"pmid":"16221754","species":"human","arm":"","form":"Biaxin (Abbott)","forms":[],"dose":"500 mg twice daily mg","doseBasis":"NR","fed":"as above","n":"16","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-3h","value":"4.5","variance":"± 1.2 (SD)","units":"ng/h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-clarithromycin. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"Biaxin (Abbott)","forms":[],"dose":"500 mg twice daily mg","doseBasis":"NR","fed":"as above","n":"16","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-24h","value":"13.4","variance":"± 3.1 (SD)","units":"ng/h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-clarithromycin. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"Biaxin (Abbott)","forms":[],"dose":"500 mg twice daily mg","doseBasis":"NR","fed":"as above","n":"16","analyte":"digoxin","matrix":"serum","parameter":"Cmax","detail":"","value":"2.9","variance":"± 0.9 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-clarithromycin. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"Rifadin (Aventis)","forms":[],"dose":"300 mg twice daily mg","doseBasis":"NR","fed":"as above","n":"16","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-3h","value":"5.2","variance":"± 1.2 (SD)","units":"ng/h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-rifampin. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"Rifadin (Aventis)","forms":[],"dose":"300 mg twice daily mg","doseBasis":"NR","fed":"as above","n":"16","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-24h","value":"14.7","variance":"± 2.7 (SD)","units":"ng/h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-rifampin. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"Rifadin (Aventis)","forms":[],"dose":"300 mg twice daily mg","doseBasis":"NR","fed":"as above","n":"16","analyte":"digoxin","matrix":"serum","parameter":"Cmax","detail":"","value":"3.5","variance":"± 1.1 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-rifampin. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"Milk thistle softgel capsule, standardized to 80% silymarin (Enzymatic Therapy, lot 41678) (Enzymatic Therapy)","forms":["silymarin"],"dose":"300 mg three times daily (900 mg daily) mg","doseBasis":"salt/compound","fed":"digoxin given after overnight fast; meal 4 h post-dose","n":"16","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-3h","value":"4.8","variance":"± 1.4 (SD)","units":"ng/h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-milk thistle. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"Milk thistle softgel capsule, standardized to 80% silymarin (Enzymatic Therapy, lot 41678) (Enzymatic Therapy)","forms":["silymarin"],"dose":"300 mg three times daily (900 mg daily) mg","doseBasis":"salt/compound","fed":"digoxin given after overnight fast; meal 4 h post-dose","n":"16","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-24h","value":"13.8","variance":"± 3.1 (SD)","units":"ng/h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-milk thistle. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"Milk thistle softgel capsule, standardized to 80% silymarin (Enzymatic Therapy, lot 41678) (Enzymatic Therapy)","forms":["silymarin"],"dose":"300 mg three times daily (900 mg daily) mg","doseBasis":"salt/compound","fed":"digoxin given after overnight fast; meal 4 h post-dose","n":"16","analyte":"digoxin","matrix":"serum","parameter":"Cmax","detail":"","value":"3.0","variance":"± 1.0 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-milk thistle. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"Black cohosh extract tablet, 2.5% triterpene glycosides (Enzymatic Therapy, lot 41924) (Enzymatic Therapy)","forms":[],"dose":"20 mg twice daily mg","doseBasis":"salt/compound","fed":"as above","n":"16","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-3h","value":"4.5","variance":"± 1.0 (SD)","units":"ng/h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-black cohosh. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"Black cohosh extract tablet, 2.5% triterpene glycosides (Enzymatic Therapy, lot 41924) (Enzymatic Therapy)","forms":[],"dose":"20 mg twice daily mg","doseBasis":"salt/compound","fed":"as above","n":"16","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-24h","value":"13.2","variance":"± 3.1 (SD)","units":"ng/h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-black cohosh. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"Black cohosh extract tablet, 2.5% triterpene glycosides (Enzymatic Therapy, lot 41924) (Enzymatic Therapy)","forms":[],"dose":"20 mg twice daily mg","doseBasis":"salt/compound","fed":"as above","n":"16","analyte":"digoxin","matrix":"serum","parameter":"Cmax","detail":"","value":"2.8","variance":"± 1.1 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Row label: Pre-black cohosh. Off-target analyte (digoxin, not milk thistle)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-3h baseline by ABCB1 haplotype GC-TT","value":"5.0","variance":"± 1.4 (SD)","units":"ng/h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-24h baseline by ABCB1 haplotype GC-TT","value":"15.1","variance":"± 3.7 (SD)","units":"ng/h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"Cmax","detail":"Cmax baseline by ABCB1 haplotype GC-TT","value":"2.7","variance":"± 1.0 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-3h baseline by ABCB1 haplotype GC-GC","value":"4.2","variance":"± 1.1 (SD)","units":"ng/h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-24h baseline by ABCB1 haplotype GC-GC","value":"12.6","variance":"± 3.1 (SD)","units":"ng/h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"Cmax","detail":"Cmax baseline by ABCB1 haplotype GC-GC","value":"3.1","variance":"± 1.1 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-3h baseline by ABCB1 haplotype GT-TT","value":"4.8","variance":"± 1.1 (SD)","units":"ng/h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-24h baseline by ABCB1 haplotype GT-TT","value":"13.9","variance":"± 3.3 (SD)","units":"ng/h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"Cmax","detail":"Cmax baseline by ABCB1 haplotype GT-TT","value":"3.4","variance":"± 0.9 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-3h baseline by ABCB1 haplotype GC-GT","value":"4.7","variance":"± 0.8 (SD)","units":"ng/h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-24h baseline by ABCB1 haplotype GC-GT","value":"12.7","variance":"± 1.3 (SD)","units":"ng/h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"Cmax","detail":"Cmax baseline by ABCB1 haplotype GC-GT","value":"3.1","variance":"± 0.7 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-3h baseline by ABCB1 haplotype TT-TT","value":"4.9","variance":"± 1.4 (SD)","units":"ng/h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"AUC","detail":"AUC0-24h baseline by ABCB1 haplotype TT-TT","value":"13.5","variance":"± 2.4 (SD)","units":"ng/h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin)."},{"pmid":"16221754","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"digoxin","matrix":"serum","parameter":"Cmax","detail":"Cmax baseline by ABCB1 haplotype TT-TT","value":"3.3","variance":"± 6.1 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"ABCB1 haplotype subgroup; off-target analyte (digoxin). SD printed as 6.1 for Cmax in TT-TT, as printed."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 1 (max over 48-h sampling period)","value":"101","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 1 (max over 48-h sampling period)","value":"27.6","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 2 (max over 48-h sampling period)","value":"23.6","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 2 (max over 48-h sampling period)","value":"23.9","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 3 (max over 48-h sampling period)","value":"24.2","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 3 (max over 48-h sampling period)","value":"14.2","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 4 (max over 48-h sampling period)","value":"124","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 4 (max over 48-h sampling period)","value":"89.6","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 5 (max over 48-h sampling period)","value":"12.3","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 5 (max over 48-h sampling period)","value":"31.8","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 6 (max over 48-h sampling period)","value":"48.2","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"steady-state maximum plasma concentration (Css,max), patient 6 (max over 48-h sampling period)","value":"36.2","variance":"","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"Css,max mean of 6 patients","value":"55.5","variance":"± 46.2 (SD)","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"Css,max mean of 6 patients","value":"37.2","variance":"± 26.7 (SD)","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16278402","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"range of maximum silybin plasma concentrations at steady state","value":"0.0249-0.257","variance":"","units":"µmol/L","location":"Abstract / Results p.5","quote":"The maximum plasma concentrations of silybin ranged between 0.0249 and 0.257 Amol/L.","quoteCheck":"value not in quote","note":"Abstract prints 'Amol/L' (text layer for µmol/L); page image shows µmol/L. Value is a range only; recorded in range field. Results text: 'ranged between 0.0249 and 0.257 µmol/L' and 'f10-fold' variable (~10-fold)."},{"pmid":"16278402","species":"human","arm":"","form":"none (irinotecan alone)","forms":[],"dose":"mg","doseBasis":"NR","fed":"NR","n":"6","analyte":"Irinotecan (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.82","variance":"± 0.852 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"Irinotecan (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.96","variance":"± 0.593 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"Irinotecan (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.88","variance":"± 0.647 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"none (irinotecan alone)","forms":[],"dose":"mg","doseBasis":"NR","fed":"NR","n":"6","analyte":"Irinotecan (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC (extrapolated to infinity)","value":"9.15","variance":"± 3.93 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"Irinotecan (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC (extrapolated to infinity)","value":"10.6","variance":"± 3.84 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"Irinotecan (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC (extrapolated to infinity)","value":"10.4","variance":"± 3.73 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"none (irinotecan alone)","forms":[],"dose":"mg","doseBasis":"NR","fed":"NR","n":"6","analyte":"SN-38 (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"37.1","variance":"± 31.5 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"SN-38 (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"31.0","variance":"± 16.6 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"SN-38 (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"29.6","variance":"± 17.4 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"none (irinotecan alone)","forms":[],"dose":"mg","doseBasis":"NR","fed":"NR","n":"6","analyte":"SN-38 (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC","value":"239","variance":"± 154 (SD)","units":"ng·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"SN-38 (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC","value":"233","variance":"± 151 (SD)","units":"ng·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"SN-38 (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC","value":"226","variance":"± 136 (SD)","units":"ng·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"none (irinotecan alone)","forms":[],"dose":"mg","doseBasis":"NR","fed":"NR","n":"6","analyte":"SN-38G (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.234","variance":"± 0.204 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"SN-38G (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.222","variance":"± 0.091 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"SN-38G (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.240","variance":"± 0.104 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"none (irinotecan alone)","forms":[],"dose":"mg","doseBasis":"NR","fed":"NR","n":"6","analyte":"SN-38G (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC","value":"2.47","variance":"± 1.76 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"SN-38G (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC","value":"2.44","variance":"± 1.09 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"SN-38G (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC","value":"2.18","variance":"± 0.854 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"none (irinotecan alone)","forms":[],"dose":"mg","doseBasis":"NR","fed":"NR","n":"6","analyte":"APC (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.294","variance":"± 0.233 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"APC (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.302","variance":"± 0.169 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"APC (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.381","variance":"± 0.241 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"none (irinotecan alone)","forms":[],"dose":"mg","doseBasis":"NR","fed":"NR","n":"6","analyte":"APC (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC","value":"3.01","variance":"± 2.07 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"APC (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC","value":"3.11","variance":"± 2.10 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16278402","species":"human","arm":"","form":"Milk thistle seed extract capsules (80% silymarin), GNC, lot 4603KC3918 (GNC)","forms":["silymarin"],"dose":"200 mg capsule, thrice per day (one with each meal) mg","doseBasis":"salt/compound","fed":"with meals","n":"6","analyte":"APC (co-administered irinotecan or metabolite; not silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC","value":"3.46","variance":"± 2.18 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (irinotecan/metabolite PK; drug interaction outcome). Units verified from page image (µg/mL etc.); text layer shows A for µ."},{"pmid":"16432272","species":"human","arm":"","form":"Biaxin (Abbott)","forms":[],"dose":"500 mg twice daily (1000 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"AUC","detail":"AUC0-inf","value":"89.6","variance":"± 30.6 (SD)","units":"ng/h/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Preclarithromycin. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"16432272","species":"human","arm":"","form":"Biaxin (Abbott)","forms":[],"dose":"500 mg twice daily (1000 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"Cmax","detail":"","value":"31.8","variance":"± 11.6 (SD)","units":"ng/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Preclarithromycin. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"16432272","species":"human","arm":"","form":"Biaxin (Abbott)","forms":[],"dose":"500 mg twice daily (1000 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"Tmax","detail":"","value":"0.54","variance":"± 0.25 (SD)","units":"h","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Preclarithromycin. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"16432272","species":"human","arm":"","form":"Rifadin (Aventis)","forms":[],"dose":"300 mg twice daily (600 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"AUC","detail":"AUC0-inf","value":"79.6","variance":"± 23.2 (SD)","units":"ng/h/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Prerifampin. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"16432272","species":"human","arm":"","form":"Rifadin (Aventis)","forms":[],"dose":"300 mg twice daily (600 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"Cmax","detail":"","value":"30.6","variance":"± 14.6 (SD)","units":"ng/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Prerifampin. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"16432272","species":"human","arm":"","form":"Rifadin (Aventis)","forms":[],"dose":"300 mg twice daily (600 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"Tmax","detail":"","value":"0.64","variance":"± 0.32 (SD)","units":"h","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Prerifampin. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"16432272","species":"human","arm":"","form":"softgel capsule standardized to 80% silymarin (lot 41678) (Enzymatic Therapy)","forms":["silymarin"],"dose":"300 mg three times daily (900 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"AUC","detail":"AUC0-inf","value":"96.2","variance":"± 42.2 (SD)","units":"ng/h/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Pre-milk thistle. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"16432272","species":"human","arm":"","form":"softgel capsule standardized to 80% silymarin (lot 41678) (Enzymatic Therapy)","forms":["silymarin"],"dose":"300 mg three times daily (900 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"Cmax","detail":"","value":"37.2","variance":"± 18.1 (SD)","units":"ng/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Pre-milk thistle. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"16432272","species":"human","arm":"","form":"softgel capsule standardized to 80% silymarin (lot 41678) (Enzymatic Therapy)","forms":["silymarin"],"dose":"300 mg three times daily (900 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"Tmax","detail":"","value":"0.47","variance":"± 0.24 (SD)","units":"h","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Pre-milk thistle. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"16432272","species":"human","arm":"","form":"uncoated tablet, 2.5% triterpene glycosides (lot 41924) (Enzymatic Therapy)","forms":[],"dose":"40 mg twice daily (80 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"AUC","detail":"AUC0-inf","value":"94.8","variance":"± 29.2 (SD)","units":"ng/h/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Pre-black cohosh. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"16432272","species":"human","arm":"","form":"uncoated tablet, 2.5% triterpene glycosides (lot 41924) (Enzymatic Therapy)","forms":[],"dose":"40 mg twice daily (80 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"Cmax","detail":"","value":"34.6","variance":"± 15.5 (SD)","units":"ng/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Pre-black cohosh. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"16432272","species":"human","arm":"","form":"uncoated tablet, 2.5% triterpene glycosides (lot 41924) (Enzymatic Therapy)","forms":[],"dose":"40 mg twice daily (80 mg/day) mg","doseBasis":"NR","fed":"midazolam after overnight fast; identical meal 4 h post-dose","n":"19","analyte":"midazolam","matrix":"serum","parameter":"Tmax","detail":"","value":"0.64","variance":"± 0.30 (SD)","units":"h","location":"Table I","quote":"","quoteCheck":"no quote","note":"Row label: Pre-black cohosh. Off-target analyte (midazolam, not milk thistle)."},{"pmid":"17077998","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"some individual peak plasma levels exceeded 100 µM; highest levels at 13 g dose level","value":">100","variance":"","units":"µM","location":"Discussion","quote":"While some peak plasma levels of silibinin were in excess of 100 µM","quoteCheck":"value not in quote","note":"Qualitative statement; no dose-response above 13 g."},{"pmid":"17315537","species":"human","arm":"","form":"Silybin-phosphatidylcholine complex capsules (silybinin capsules) (Tianjin Tasly Pharmaceutical Co. Ltd.)","forms":["phytosome"],"dose":"280 mg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"overnight fast; remained fasting for 4 h after dosing","n":"20","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"4242.1","variance":"± 2252.9 (SD)","units":"ng·ml-1","location":"Table III","quote":"Data were expressed as mean±S.D.","quoteCheck":"value not in quote","note":""},{"pmid":"17315537","species":"human","arm":"","form":"Silybin-phosphatidylcholine complex capsules (silybinin capsules) (Tianjin Tasly Pharmaceutical Co. Ltd.)","forms":["phytosome"],"dose":"280 mg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"overnight fast; remained fasting for 4 h after dosing","n":"20","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.40","variance":"± 0.55 (SD)","units":"h","location":"Table III","quote":"","quoteCheck":"no quote","note":"Summary states Tmax mean 1.4 h, range 0.67-2.67 h."},{"pmid":"17315537","species":"human","arm":"","form":"Silybin-phosphatidylcholine complex capsules (silybinin capsules) (Tianjin Tasly Pharmaceutical Co. Ltd.)","forms":["phytosome"],"dose":"280 mg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"overnight fast; remained fasting for 4 h after dosing","n":"20","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"5870.6","variance":"± 1894.8 (SD)","units":"ng·h·ml-1","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17315537","species":"human","arm":"","form":"Silybin-phosphatidylcholine complex capsules (silybinin capsules) (Tianjin Tasly Pharmaceutical Co. Ltd.)","forms":["phytosome"],"dose":"280 mg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"overnight fast; remained fasting for 4 h after dosing","n":"20","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"5946.6","variance":"± 1898.9 (SD)","units":"ng·h·ml-1","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17315537","species":"human","arm":"","form":"Silybin-phosphatidylcholine complex capsules (silybinin capsules) (Tianjin Tasly Pharmaceutical Co. Ltd.)","forms":["phytosome"],"dose":"280 mg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"overnight fast; remained fasting for 4 h after dosing","n":"20","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"Tmax range across subjects","value":"0.67-2.67","variance":"","units":"h","location":"Summary / Discussion","quote":"the times to reach peak plasma concentration (Tmax) ranged from 0.67 to 2.67h, and the mean was 1.4h","quoteCheck":"value not in quote","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silychristin (SC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"N.D.","variance":"","units":"ng/ml","location":"Table 2","quote":"SC Free N.D.","quoteCheck":"supported","note":"N.D., not detected (as printed)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silychristin (SC)","matrix":"plasma","parameter":"Tmax","detail":"","value":"N.D.","variance":"","units":"h","location":"Table 2","quote":"SC Free N.D.","quoteCheck":"supported","note":"N.D., not detected (as printed)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silychristin (SC)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"N.D.","variance":"","units":"µg·h/l","location":"Table 2","quote":"SC Free N.D.","quoteCheck":"supported","note":"N.D., not detected (as printed)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silychristin (SC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"37","variance":"± 7.8 (SD)","units":"ng/ml","location":"Table 2","quote":"SC Total Cmax 37 ± 7.8","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silychristin (SC)","matrix":"plasma","parameter":"Tmax","detail":"","value":"3.7","variance":"± 0.6 (SD)","units":"h","location":"Table 2","quote":"SC Total Tmax 3.7 ± 0.6","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silychristin (SC)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"401","variance":"± 93 (SD)","units":"µg·h/l","location":"Table 2","quote":"SC Total AUC0-inf 401 ± 93","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silychristin (SC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"37","variance":"± 7.8 (SD)","units":"ng/ml","location":"Table 2","quote":"SC Conjugated Cmax 37 ± 7.8","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silychristin (SC)","matrix":"plasma","parameter":"Tmax","detail":"","value":"3.7","variance":"± 0.6 (SD)","units":"h","location":"Table 2","quote":"SC Conjugated Tmax 3.7 ± 0.6","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silychristin (SC)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"401","variance":"± 93 (SD)","units":"µg·h/l","location":"Table 2","quote":"SC Conjugated AUC0-inf 401 ± 93","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silydianin (SD)","matrix":"plasma","parameter":"Cmax","detail":"","value":"N.D.","variance":"","units":"ng/ml","location":"Table 2","quote":"SD Free N.D.","quoteCheck":"supported","note":"N.D., not detected (as printed)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silydianin (SD)","matrix":"plasma","parameter":"Tmax","detail":"","value":"N.D.","variance":"","units":"h","location":"Table 2","quote":"SD Free N.D.","quoteCheck":"supported","note":"N.D., not detected (as printed)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silydianin (SD)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"N.D.","variance":"","units":"µg·h/l","location":"Table 2","quote":"SD Free N.D.","quoteCheck":"supported","note":"N.D., not detected (as printed)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silydianin (SD)","matrix":"plasma","parameter":"Cmax","detail":"","value":"21","variance":"± 3.1 (SD)","units":"ng/ml","location":"Table 2","quote":"SD Total Cmax 21 ± 3.1","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silydianin (SD)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.8","variance":"± 1.3 (SD)","units":"h","location":"Table 2","quote":"SD Total Tmax 2.8 ± 1.3","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silydianin (SD)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"140","variance":"± 47 (SD)","units":"µg·h/l","location":"Table 2","quote":"SD Total AUC0-inf 140 ± 47","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silydianin (SD)","matrix":"plasma","parameter":"Cmax","detail":"","value":"21","variance":"± 3.1 (SD)","units":"ng/ml","location":"Table 2","quote":"SD Conjugated Cmax 21 ± 3.1","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silydianin (SD)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.8","variance":"± 1.3 (SD)","units":"h","location":"Table 2","quote":"SD Conjugated Tmax 2.8 ± 1.3","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silydianin (SD)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"140","variance":"± 47 (SD)","units":"µg·h/l","location":"Table 2","quote":"SD Conjugated AUC0-inf 140 ± 47","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silybin A (SBA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"23","variance":"± 7.9 (SD)","units":"ng/ml","location":"Table 2","quote":"SBA Free Cmax 23 ± 7.9","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silybin A (SBA)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.0","variance":"± 0.4 (SD)","units":"h","location":"Table 2","quote":"SBA Free Tmax 1.0 ± 0.4","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silybin A (SBA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"63","variance":"± 38 (SD)","units":"µg·h/l","location":"Table 2","quote":"SBA Free AUC0-inf 63 ± 38","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silybin A (SBA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"45","variance":"± 16 (SD)","units":"ng/ml","location":"Table 2","quote":"SBA Total Cmax 45 ± 16","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silybin A (SBA)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.3","variance":"± 0.3 (SD)","units":"h","location":"Table 2","quote":"SBA Total Tmax 1.3 ± 0.3","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silybin A (SBA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"260","variance":"± 95 (SD)","units":"µg·h/l","location":"Table 2","quote":"SBA Total AUC0-inf 260 ± 95","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silybin A (SBA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"26","variance":"± 6.8 (SD)","units":"ng/ml","location":"Table 2","quote":"SBA Conjugated Cmax 26 ± 6.8","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silybin A (SBA)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.2","variance":"± 0.8 (SD)","units":"h","location":"Table 2","quote":"SBA Conjugated Tmax 2.2 ± 0.8","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silybin A (SBA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"208","variance":"± 65 (SD)","units":"µg·h/l","location":"Table 2","quote":"SBA Conjugated AUC0-inf 208 ± 65","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silybin B (SBB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"15","variance":"± 7.4 (SD)","units":"ng/ml","location":"Table 2","quote":"SBB Free Cmax 15 ± 7.4","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silybin B (SBB)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.83","variance":"± 0.1 (SD)","units":"h","location":"Table 2","quote":"SBB Free Tmax 0.83 ± 0.1","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free silybin B (SBB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"51","variance":"± 19 (SD)","units":"µg·h/l","location":"Table 2","quote":"SBB Free AUC0-inf 51 ± 19","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silybin B (SBB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"131","variance":"± 28 (SD)","units":"ng/ml","location":"Table 2","quote":"SBB Total Cmax 131 ± 28","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silybin B (SBB)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.3","variance":"± 0.3 (SD)","units":"h","location":"Table 2","quote":"SBB Total Tmax 1.3 ± 0.3","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total silybin B (SBB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"647","variance":"± 234 (SD)","units":"µg·h/l","location":"Table 2","quote":"SBB Total AUC0-inf 647 ± 234","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silybin B (SBB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"118","variance":"± 21 (SD)","units":"ng/ml","location":"Table 2","quote":"SBB Conjugated Cmax 118 ± 21","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silybin B (SBB)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.5","variance":"± 0.5 (SD)","units":"h","location":"Table 2","quote":"SBB Conjugated Tmax 1.5 ± 0.5","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated silybin B (SBB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"597","variance":"± 204 (SD)","units":"µg·h/l","location":"Table 2","quote":"SBB Conjugated AUC0-inf 597 ± 204","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free isosilybin A (ISBA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"9.7","variance":"± 4.8 (SD)","units":"ng/ml","location":"Table 2","quote":"ISBA Free Cmax 9.7 ± 4.8","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free isosilybin A (ISBA)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.75","variance":"± 0.3 (SD)","units":"h","location":"Table 2","quote":"ISBA Free Tmax 0.75 ± 0.3","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free isosilybin A (ISBA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"30","variance":"± 8 (SD)","units":"µg·h/l","location":"Table 2","quote":"ISBA Free AUC0-inf 30 ± 8","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total isosilybin A (ISBA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"113","variance":"± 30 (SD)","units":"ng/ml","location":"Table 2","quote":"ISBA Total Cmax 113 ± 30","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total isosilybin A (ISBA)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.7","variance":"± 0.3 (SD)","units":"h","location":"Table 2","quote":"ISBA Total Tmax 1.7 ± 0.3","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total isosilybin A (ISBA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"799","variance":"± 403 (SD)","units":"µg·h/l","location":"Table 2","quote":"ISBA Total AUC0-inf 799 ± 403","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated isosilybin A (ISBA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"108","variance":"± 30 (SD)","units":"ng/ml","location":"Table 2","quote":"ISBA Conjugated Cmax 108 ± 30","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated isosilybin A (ISBA)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.5","variance":"± 1.3 (SD)","units":"h","location":"Table 2","quote":"ISBA Conjugated Tmax 2.5 ± 1.3","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated isosilybin A (ISBA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"734","variance":"± 346 (SD)","units":"µg·h/l","location":"Table 2","quote":"ISBA Conjugated AUC0-inf 734 ± 346","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free isosilybin B (ISBB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"8.5","variance":"± 4.4 (SD)","units":"ng/ml","location":"Table 2","quote":"ISBB Free Cmax 8.5 ± 4.4","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free isosilybin B (ISBB)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.75","variance":"± 0.3 (SD)","units":"h","location":"Table 2","quote":"ISBB Free Tmax 0.75 ± 0.3","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"free isosilybin B (ISBB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"26","variance":"± 12 (SD)","units":"µg·h/l","location":"Table 2","quote":"ISBB Free AUC0-inf 26 ± 12","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total isosilybin B (ISBB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"59","variance":"± 16 (SD)","units":"ng/ml","location":"Table 2","quote":"ISBB Total Cmax 59 ± 16","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total isosilybin B (ISBB)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.5","variance":"± 0.0 (SD)","units":"h","location":"Table 2","quote":"ISBB Total Tmax 1.5 ± 0.0","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"total isosilybin B (ISBB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"383","variance":"± 195 (SD)","units":"µg·h/l","location":"Table 2","quote":"ISBB Total AUC0-inf 383 ± 195","quoteCheck":"supported","note":""},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated isosilybin B (ISBB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"53","variance":"± 13 (SD)","units":"ng/ml","location":"Table 2","quote":"ISBB Conjugated Cmax 53 ± 13","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated isosilybin B (ISBB)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.5","variance":"± 0.9 (SD)","units":"h","location":"Table 2","quote":"ISBB Conjugated Tmax 2.5 ± 0.9","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"17913795","species":"human","arm":"","form":"milk thistle extract capsules (2 x 300 mg labeled) (Nutraceutical Sciences Institute (capsule 1))","forms":["silymarin"],"dose":"600 mg extract","doseBasis":"salt/compound","fed":"NR","n":"3","analyte":"conjugated isosilybin B (ISBB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"355","variance":"± 170 (SD)","units":"µg·h/l","location":"Table 2","quote":"ISBB Conjugated AUC0-inf 355 ± 170","quoteCheck":"supported","note":"Conjugated = calculated from total minus free (per Methods)"},{"pmid":"18054294","species":"human","arm":"","form":"silybin-phosphatidylcholine complex (Tianjin Tasly Pharmaceutical Co.)","forms":["phytosome"],"dose":"280 mg silybin (133 mg silybin A + 147 mg silybin B)","doseBasis":"active compound","fed":"overnight fast, fasted 4 h after dosing","n":"22","analyte":"silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"2333.7","variance":"± 1037.1 (NR)","units":"ng/ml","location":"Table 3","quote":"Cmax silybin A: 2333.7 ± 1037.1 ng/ml","quoteCheck":"supported","note":"± value as printed; type of mean/variance not stated"},{"pmid":"18054294","species":"human","arm":"","form":"silybin-phosphatidylcholine complex (Tianjin Tasly Pharmaceutical Co.)","forms":["phytosome"],"dose":"280 mg silybin (133 mg silybin A + 147 mg silybin B)","doseBasis":"active compound","fed":"overnight fast, fasted 4 h after dosing","n":"22","analyte":"silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"582.4","variance":"± 350.3 (NR)","units":"ng/ml","location":"Table 3","quote":"Cmax silybin B: 582.4 ± 350.3 ng/ml","quoteCheck":"supported","note":"± value as printed; type of mean/variance not stated"},{"pmid":"18054294","species":"human","arm":"","form":"silybin-phosphatidylcholine complex (Tianjin Tasly Pharmaceutical Co.)","forms":["phytosome"],"dose":"280 mg silybin (133 mg silybin A + 147 mg silybin B)","doseBasis":"active compound","fed":"overnight fast, fasted 4 h after dosing","n":"22","analyte":"silybin A","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.46","variance":"± 0.60 (NR)","units":"h","location":"Table 3","quote":"Tmax silybin A: 1.46 ± 0.60 h","quoteCheck":"supported","note":"± value as printed; type of mean/variance not stated"},{"pmid":"18054294","species":"human","arm":"","form":"silybin-phosphatidylcholine complex (Tianjin Tasly Pharmaceutical Co.)","forms":["phytosome"],"dose":"280 mg silybin (133 mg silybin A + 147 mg silybin B)","doseBasis":"active compound","fed":"overnight fast, fasted 4 h after dosing","n":"22","analyte":"silybin B","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.36","variance":"± 0.58 (NR)","units":"h","location":"Table 3","quote":"Tmax silybin B: 1.36 ± 0.58 h","quoteCheck":"supported","note":"± value as printed; type of mean/variance not stated"},{"pmid":"18054294","species":"human","arm":"","form":"silybin-phosphatidylcholine complex (Tianjin Tasly Pharmaceutical Co.)","forms":["phytosome"],"dose":"280 mg silybin (133 mg silybin A + 147 mg silybin B)","doseBasis":"active compound","fed":"overnight fast, fasted 4 h after dosing","n":"22","analyte":"silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"3495.7","variance":"± 1007.5 (NR)","units":"ng/ml h","location":"Table 3","quote":"AUC silybin A: 3495.7 ± 1007.5 ng/ml h","quoteCheck":"supported","note":"± value as printed; type of mean/variance not stated"},{"pmid":"18054294","species":"human","arm":"","form":"silybin-phosphatidylcholine complex (Tianjin Tasly Pharmaceutical Co.)","forms":["phytosome"],"dose":"280 mg silybin (133 mg silybin A + 147 mg silybin B)","doseBasis":"active compound","fed":"overnight fast, fasted 4 h after dosing","n":"22","analyte":"silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"780.4","variance":"± 301.0 (NR)","units":"ng/ml h","location":"Table 3","quote":"AUC silybin B: 780.4 ± 301.0 ng/ml h","quoteCheck":"supported","note":"± value as printed; type of mean/variance not stated"},{"pmid":"18054294","species":"human","arm":"","form":"silybin-phosphatidylcholine complex (Tianjin Tasly Pharmaceutical Co.)","forms":["phytosome"],"dose":"280 mg silybin (133 mg silybin A + 147 mg silybin B)","doseBasis":"active compound","fed":"overnight fast, fasted 4 h after dosing","n":"22","analyte":"silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"3580.8","variance":"± 1007.2 (NR)","units":"ng/ml h","location":"Table 3","quote":"AUC silybin A: 3580.8 ± 1007.2 ng/ml h","quoteCheck":"supported","note":"± value as printed; type of mean/variance not stated"},{"pmid":"18054294","species":"human","arm":"","form":"silybin-phosphatidylcholine complex (Tianjin Tasly Pharmaceutical Co.)","forms":["phytosome"],"dose":"280 mg silybin (133 mg silybin A + 147 mg silybin B)","doseBasis":"active compound","fed":"overnight fast, fasted 4 h after dosing","n":"22","analyte":"silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"886.3","variance":"± 288.7 (NR)","units":"ng/ml h","location":"Table 3","quote":"AUC silybin B: 886.3 ± 288.7 ng/ml h","quoteCheck":"supported","note":"± value as printed; type of mean/variance not stated"},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"parent (unconjugated) silybin A (SA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"12","variance":"","units":"ng/ml","location":"Table 2","quote":"12 (2, 67)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"parent (unconjugated) silybin A (SA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"33","variance":"","units":"ng·h/ml","location":"Table 2","quote":"33 (2, 488)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"total (parent + conjugated) silybin A (SA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"37","variance":"","units":"ng/ml","location":"Table 3","quote":"37 (23, 61)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"total (parent + conjugated) silybin A (SA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"256","variance":"","units":"ng·h/ml","location":"Table 3","quote":"256 (118, 557)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"parent (unconjugated) silybin B (SB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"9","variance":"","units":"ng/ml","location":"Table 2","quote":"9 (2, 43)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"parent (unconjugated) silybin B (SB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"23","variance":"","units":"ng·h/ml","location":"Table 2","quote":"23 (2, 302)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"total (parent + conjugated) silybin B (SB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"106","variance":"","units":"ng/ml","location":"Table 3","quote":"106 (63, 177)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"total (parent + conjugated) silybin B (SB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"617","variance":"","units":"ng·h/ml","location":"Table 3","quote":"617 (327, 1164)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"parent (unconjugated) isosilybin A (ISA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"3","variance":"","units":"ng/ml","location":"Table 2","quote":"3 (1, 14)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"parent (unconjugated) isosilybin A (ISA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"3","variance":"","units":"ng·h/ml","location":"Table 2","quote":"3 (1, 16)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"total (parent + conjugated) isosilybin A (ISA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"71","variance":"","units":"ng/ml","location":"Table 3","quote":"71 (32, 157)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% 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(below limit of quantitation)","quoteCheck":"supported","note":"Not determined (N.D.): concentrations below limit of quantitation (as printed); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"parent (unconjugated) isosilybin B (ISB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"N.D.","variance":"","units":"ng·h/ml","location":"Table 2","quote":"N.D. (below limit of quantitation)","quoteCheck":"supported","note":"Not determined (N.D.): concentrations below limit of quantitation (as printed); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"total (parent + conjugated) isosilybin B (ISB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"41","variance":"","units":"ng/ml","location":"Table 3","quote":"41 (21, 80)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"total (parent + conjugated) isosilybin B (ISB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"251","variance":"","units":"ng·h/ml","location":"Table 3","quote":"251 (145, 436)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"parent (unconjugated) silychristin (SC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"N.D.","variance":"","units":"ng/ml","location":"Table 2","quote":"N.D. (below limit of quantitation)","quoteCheck":"supported","note":"Not determined (N.D.): concentrations below limit of quantitation (as printed); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"parent (unconjugated) silychristin (SC)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"N.D.","variance":"","units":"ng·h/ml","location":"Table 2","quote":"N.D. (below limit of quantitation)","quoteCheck":"supported","note":"Not determined (N.D.): concentrations below limit of quantitation (as printed); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"total (parent + conjugated) silychristin (SC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"37","variance":"","units":"ng/ml","location":"Table 3","quote":"37 (18, 76)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"total (parent + conjugated) silychristin (SC)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"355","variance":"","units":"ng·h/ml","location":"Table 3","quote":"355 (169, 745)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"parent (unconjugated) silydianin (SD)","matrix":"plasma","parameter":"Cmax","detail":"","value":"N.D.","variance":"","units":"ng/ml","location":"Table 2","quote":"N.D. (below limit of quantitation)","quoteCheck":"supported","note":"Not determined (N.D.): concentrations below limit of quantitation (as printed); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"parent (unconjugated) silydianin (SD)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"N.D.","variance":"","units":"ng·h/ml","location":"Table 2","quote":"N.D. (below limit of quantitation)","quoteCheck":"supported","note":"Not determined (N.D.): concentrations below limit of quantitation (as printed); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"total (parent + conjugated) silydianin (SD)","matrix":"plasma","parameter":"Cmax","detail":"","value":"12","variance":"","units":"ng/ml","location":"Table 3","quote":"12 (2, 64)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"total (parent + conjugated) silydianin (SD)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"51","variance":"","units":"ng·h/ml","location":"Table 3","quote":"51 (3, 807)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"parent (unconjugated) silybin A (SA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"13","variance":"","units":"ng/ml","location":"Table 2","quote":"13 (1, 269)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"parent (unconjugated) silybin A (SA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"13","variance":"","units":"ng·h/ml","location":"Table 2","quote":"13 (1,156)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) silybin A (SA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"73","variance":"","units":"ng/ml","location":"Table 3","quote":"73 (19, 282)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) silybin A (SA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"301","variance":"","units":"ng·h/ml","location":"Table 3","quote":"301 (100, 901)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"parent (unconjugated) silybin B (SB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"12","variance":"","units":"ng/ml","location":"Table 2","quote":"12 (1, 252)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"parent (unconjugated) silybin B (SB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"16","variance":"","units":"ng·h/ml","location":"Table 2","quote":"16 (1, 397)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) silybin B (SB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"269","variance":"","units":"ng/ml","location":"Table 3","quote":"269 (73, 995)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) silybin B 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(below limit of quantitation)","quoteCheck":"supported","note":"Not determined (N.D.): concentrations below limit of quantitation (as printed); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) isosilybin A (ISA)","matrix":"plasma","parameter":"Cmax","detail":"","value":"216","variance":"","units":"ng/ml","location":"Table 3","quote":"216 (96, 485)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) isosilybin A (ISA)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"1279","variance":"","units":"ng·h/ml","location":"Table 3","quote":"1279 (690, 2371)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"parent (unconjugated) isosilybin B (ISB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"5","variance":"","units":"ng/ml","location":"Table 2","quote":"5 (0.3, 62)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"parent (unconjugated) isosilybin B (ISB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"4","variance":"","units":"ng·h/ml","location":"Table 2","quote":"4 (0.4, 51)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) isosilybin B (ISB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"137","variance":"","units":"ng/ml","location":"Table 3","quote":"137 (55, 343)*","quoteCheck":"supported","note":"* p <= 0.02, comparison with healthy cohort"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) isosilybin B (ISB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"706","variance":"","units":"ng·h/ml","location":"Table 3","quote":"706 (406, 1230)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"parent (unconjugated) silychristin (SC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"N.D.","variance":"","units":"ng/ml","location":"Table 2","quote":"N.D. (below limit of quantitation)","quoteCheck":"supported","note":"Not determined (N.D.): concentrations below limit of quantitation (as printed); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"parent (unconjugated) silychristin (SC)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"N.D.","variance":"","units":"ng·h/ml","location":"Table 2","quote":"N.D. (below limit of quantitation)","quoteCheck":"supported","note":"Not determined (N.D.): concentrations below limit of quantitation (as printed); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) silychristin (SC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"190","variance":"","units":"ng/ml","location":"Table 3","quote":"190 (100, 361)*","quoteCheck":"supported","note":"* p <= 0.02, comparison with healthy cohort"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) silychristin (SC)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"2043","variance":"","units":"ng·h/ml","location":"Table 3","quote":"2043 (1170, 3566)*","quoteCheck":"supported","note":"* p <= 0.02, comparison with healthy cohort"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"parent (unconjugated) silydianin (SD)","matrix":"plasma","parameter":"Cmax","detail":"","value":"N.D.","variance":"","units":"ng/ml","location":"Table 2","quote":"N.D. (below limit of quantitation)","quoteCheck":"supported","note":"Not determined (N.D.): concentrations below limit of quantitation (as printed); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"parent (unconjugated) silydianin (SD)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"N.D.","variance":"","units":"ng·h/ml","location":"Table 2","quote":"N.D. (below limit of quantitation)","quoteCheck":"supported","note":"Not determined (N.D.): concentrations below limit of quantitation (as printed); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) silydianin (SD)","matrix":"plasma","parameter":"Cmax","detail":"","value":"68","variance":"","units":"ng/ml","location":"Table 3","quote":"68 (43, 108)*","quoteCheck":"supported","note":"* p <= 0.02, comparison with healthy cohort"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"total (parent + conjugated) silydianin (SD)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"352","variance":"","units":"ng·h/ml","location":"Table 3","quote":"352 (252, 493)","quoteCheck":"supported","note":""},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"sum of silymarin conjugates (parent flavonolignan equivalents; total minus parent for six flavonolignans)","matrix":"plasma","parameter":"AUC","detail":"sum silymarin conjugates AUC0-24h","value":"1966","variance":"","units":"ng*h/ml","location":"Fig. 2 table inset","quote":"AUC0-24h 1966 (1018, 3797)","quoteCheck":"supported","note":"verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"sum of silymarin conjugates (parent flavonolignan equivalents; total minus parent for six flavonolignans)","matrix":"plasma","parameter":"AUC","detail":"sum silymarin conjugates AUC0-24h","value":"4675","variance":"","units":"ng*h/ml","location":"Fig. 2 table inset","quote":"AUC0-24h 4675 (1641, 13306)","quoteCheck":"supported","note":"verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"sum of silymarin conjugates (parent flavonolignan equivalents; total minus parent for six flavonolignans)","matrix":"plasma","parameter":"AUC","detail":"sum silymarin conjugates AUC0-24h","value":"9246","variance":"","units":"ng*h/ml","location":"Fig. 2 table inset","quote":"AUC0-24h 9246 (3447, 24810)*","quoteCheck":"supported","note":"* p <= 0.03 vs healthy (per Fig. 2 legend); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"same (Nutraceutical Sciences Institute)","forms":[],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"as above","n":"5","analyte":"sum of silymarin conjugates (parent flavonolignan equivalents; total minus parent for six flavonolignans)","matrix":"plasma","parameter":"AUC","detail":"sum silymarin conjugates AUC0-24h","value":"6477","variance":"","units":"ng*h/ml","location":"Fig. 2 table inset","quote":"AUC0-24h 6477 (3761, 11148)*","quoteCheck":"supported","note":"* p <= 0.03 vs healthy (per Fig. 2 legend); verified on page image (manager QA)"},{"pmid":"18566043","species":"human","arm":"","form":"milk thistle extract capsules (two 300 mg) (Nutraceutical Sciences Institute, Lot 0418901)","forms":["silymarin"],"dose":"600 mg milk thistle extract (labeled 80% silymarin)","doseBasis":"salt/compound","fed":"fasted overnight 8-12 h; low-fat meal immediately after dose","n":"5","analyte":"sum of total silymarin flavonolignans","matrix":"plasma","parameter":"AUC","detail":"sum of AUC0-24h of six total flavonolignans, healthy","value":"2021","variance":"","units":"ng·h/ml","location":"Abstract; Results p.1911","quote":"compared with healthy volunteers (AUC0-24h = 2021 ng · h/ml)","quoteCheck":"supported","note":"Different from Fig. 2 inset sum of conjugates AUC (1966) which is a separate quantity (conjugates only)"},{"pmid":"18566043","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"total flavonolignans","matrix":"plasma","parameter":"Tmax","detail":"median Tmax range across flavonolignans and cohorts","value":"0.5 to 2","variance":"","units":"h","location":"Results p.1911","quote":"median Tmax between 0.5 and 2 h for the various flavonolignans","quoteCheck":"value not in quote","note":"range of medians; per-compound values not in tables"},{"pmid":"18566043","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"total flavonolignans","matrix":"plasma","parameter":"Cmax","detail":"fold higher Cmax of total flavonolignans in patients vs healthy (range)","value":"1.8 to 6.3","variance":"","units":"fold","location":"Results p.1911","quote":"Cmax ... increased by similar extents (1.8-6.3-fold and 1.2-9.9-fold, respectively)","quoteCheck":"value not in quote","note":"author-stated range"},{"pmid":"18566043","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"total flavonolignans","matrix":"plasma","parameter":"AUC","detail":"fold higher AUC0-24h of total flavonolignans in patients vs healthy (range)","value":"1.2 to 9.9","variance":"","units":"fold","location":"Results p.1911","quote":"1.2-9.9-fold","quoteCheck":"value not in quote","note":"author-stated range"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"136","variance":"± 0, 318 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"quantifiable in 5 of 6 participants"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"16","variance":"± 0, 94 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"quantifiable in 3 of 6 participants"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"40","variance":"± 0, 296 (range)","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"quantifiable in 5 of 6 participants"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"8","variance":"± 0, 104 (range)","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"quantifiable in 3 of 6 participants"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silychristin","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silydianin","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"334","variance":"± 331, 553 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"87","variance":"± 58, 122 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"163","variance":"± 77, 261 (range)","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"53","variance":"± 17, 72 (range)","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silychristin","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silydianin","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"623","variance":"± 466, 1148 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"135","variance":"± 76, 317 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"364","variance":"± 144, 586 (range)","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"132","variance":"± 34, 174 (range)","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) isosilybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) isosilybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silychristin","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silydianin","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"1550","variance":"± 586, 2591 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"609","variance":"± 194, 1193 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"123","variance":"± 18, 233 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"222","variance":"± 72, 423 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"308","variance":"± 104, 1555 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"66","variance":"± 0, 103 (range)","units":"ng⋅h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"quantifiable in 5 of 6 participants"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"580","variance":"± 253, 1510 (range)","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; 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1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"5299","variance":"± 2249, 18 844 (range)","units":"ng⋅h/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"2540","variance":"± 723, 22 053 (range)","units":"ng⋅h/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"643","variance":"± 132, 3662 (range)","units":"ng⋅h/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"842","variance":"± 399, 1500 (range)","units":"ng/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"2090","variance":"± 975, 4020 (range)","units":"ng/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, isosilybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"1370","variance":"± 388, 3150 (range)","units":"ng/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 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breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"22 217","variance":"± 10 646, 45 355 (range)","units":"ng⋅h/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"10 123","variance":"± 3954, 20 490 (range)","units":"ng⋅h/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"7384","variance":"± 3573, 15 413 (range)","units":"ng⋅h/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"6448","variance":"± 2502, 8085 (range)","units":"ng⋅h/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"1404","variance":"± 920, 1841 (range)","units":"ng⋅h/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"2325","variance":"± 616, 3190 (range)","units":"ng/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"4260","variance":"± 1870, 8170 (range)","units":"ng/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, isosilybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"1950","variance":"± 769, 3350 (range)","units":"ng/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, isosilybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"1450","variance":"± 754, 2720 (range)","units":"ng/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silychristin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1052","variance":"± 413, 1280 (range)","units":"ng/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silydianin","matrix":"plasma","parameter":"Cmax","detail":"","value":"279","variance":"± 184, 386 (range)","units":"ng/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"213","variance":"± 0, 678 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"quantifiable in 5 of 6 participants"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"16","variance":"± 0, 187 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"quantifiable in 3 of 6 participants"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"363","variance":"± 331, 611 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"87","variance":"± 58, 122 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"671","variance":"± 493, 1275 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"135","variance":"± 76, 317 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"parent (nonconjugated) silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"ND","variance":"","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"Not detectable (below limit of quantitation or quantifiable in only 1 or 2 of 6 participants)"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"1783","variance":"± 808, 2739 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"647","variance":"± 313, 1245 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"123","variance":"± 18, 233 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"222","variance":"± 72, 423 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"308","variance":"± 104, 1555 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent (nonconjugated) silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"71","variance":"± 0, 103 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"quantifiable in 5 of 6 participants"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"2751","variance":"± 879, 11 774 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"5190","variance":"± 1660, 25 590 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"3238","variance":"± 900, 15 425 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"2120","variance":"± 825, 11 748 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"2654","variance":"± 815, 5139 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"total (parent + conjugates), as parent flavonolignan equivalents, silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-48h (steady state)","value":"378","variance":"± 0, 11 133 (range)","units":"ng⋅h/mL","location":"Table V","quote":"","quoteCheck":"no quote","note":"quantifiable in 5 of 6 participants"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 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1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"280 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"sum of all total (parent + conjugates) flavonolignans","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"19 258","variance":"± 11 261, 24 198 (range)","units":"ng⋅h/mL","location":"Table IV","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"sum of all total (parent + conjugates) flavonolignans","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"35 676","variance":"± 17 068, 95 675 (range)","units":"ng⋅h/mL","location":"Table IV","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"sum of all total (parent + conjugates) flavonolignans","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h (steady state)","value":"56 727","variance":"± 25 665, 103 809 (range)","units":"ng⋅h/mL","location":"Table IV","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 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breakfast served at least 2 h postdose","n":"6","analyte":"sum of all total (parent + conjugates) flavonolignans","matrix":"plasma","parameter":"Cmax","detail":"","value":"3018","variance":"± 2521, 4208 (range)","units":"ng/mL","location":"Table IV","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"560 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"5","analyte":"sum of all total (parent + conjugates) flavonolignans","matrix":"plasma","parameter":"Cmax","detail":"","value":"7965","variance":"± 2455, 14 133 (range)","units":"ng/mL","location":"Table IV","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"sum of all total (parent + conjugates) flavonolignans","matrix":"plasma","parameter":"Cmax","detail":"","value":"10 652","variance":"± 4132, 18 923 (range)","units":"ng/mL","location":"Table IV","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent silybin A","matrix":"plasma","parameter":"Cmax","detail":"peak (mean ± SD) at steady state","value":"703","variance":"± 459 (SD)","units":"ng/mL","location":"Results text p.444","quote":"","quoteCheck":"no quote","note":"Dose group not explicit in sentence; see trough note"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"parent silybin B","matrix":"plasma","parameter":"Cmax","detail":"peak (mean ± SD) at steady state","value":"274","variance":"± 200 (SD)","units":"ng/mL","location":"Results text p.444","quote":"","quoteCheck":"no quote","note":"Dose group not explicit in sentence; see trough note"},{"pmid":"19841158","species":"human","arm":"","form":"Silymarin hard capsules (180 mg milk thistle extract each; 1, 2, 4 or 5 capsules per dose), flavonolignan content per capsule: silybin A 23.2 mg, silybin B 32.0 mg, isosilybin A 11.8 mg, isosilybin B 6.6 mg, silychristin 24.9 mg, silydianin 29.0 mg (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"700 mg silymarin per dose (every 8 h)","doseBasis":"salt/compound","fed":"Day 8 dose with 240 mL water after overnight fast; breakfast served at least 2 h postdose","n":"6","analyte":"sum of all parent flavonolignans","matrix":"plasma","parameter":"Cmax","detail":"peak (mean ± SD)","value":"1235","variance":"± 322 (SD)","units":"ng/mL","location":"Results text p.445","quote":"","quoteCheck":"no quote","note":"'data not shown' per text; dose group not explicit"},{"pmid":"21315924","species":"human","arm":"","form":"Seralon-E capsule (120 mg SMR + 40 mg vitamin E) (Seralon-E capsules (Tiba Pharmaceuticals, Egypt))","forms":[],"dose":"120 mg","doseBasis":"NR","fed":"overnight fast","n":"2","analyte":"silymarin (SMR)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.811","variance":"","units":"µg ml−1","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 footnotes: 'Average of two measurements'; 'Mean value of two subjects'. No variance given. Units copied as printed (mg symbols as µ)."},{"pmid":"21315924","species":"human","arm":"","form":"Seralon-E capsule (120 mg SMR + 40 mg vitamin E) (Seralon-E capsules (Tiba Pharmaceuticals, Egypt))","forms":[],"dose":"120 mg","doseBasis":"NR","fed":"overnight fast","n":"2","analyte":"silymarin (SMR)","matrix":"plasma","parameter":"Cmax","detail":"","value":"2.084","variance":"","units":"µg ml−1","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 footnotes: 'Average of two measurements'; 'Mean value of two subjects'. No variance given. Units copied as printed (mg symbols as µ)."},{"pmid":"21315924","species":"human","arm":"","form":"Seralon-E capsule (120 mg SMR + 40 mg vitamin E) (Seralon-E capsules (Tiba Pharmaceuticals, Egypt))","forms":[],"dose":"120 mg","doseBasis":"NR","fed":"overnight fast","n":"2","analyte":"silymarin (SMR)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.0","variance":"","units":"h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 footnotes: 'Average of two measurements'; 'Mean value of two subjects'. No variance given. Units copied as printed (mg symbols as µ)."},{"pmid":"21315924","species":"human","arm":"","form":"Seralon-E capsule (120 mg SMR + 40 mg vitamin E) (Seralon-E capsules (Tiba Pharmaceuticals, Egypt))","forms":[],"dose":"120 mg","doseBasis":"NR","fed":"overnight fast","n":"2","analyte":"silymarin (SMR)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.0","variance":"","units":"h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 footnotes: 'Average of two measurements'; 'Mean value of two subjects'. No variance given. 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Units copied as printed (mg symbols as µ)."},{"pmid":"21315924","species":"human","arm":"","form":"Seralon-E capsule (120 mg SMR + 40 mg vitamin E) (Seralon-E capsules (Tiba Pharmaceuticals, Egypt))","forms":[],"dose":"120 mg","doseBasis":"NR","fed":"overnight fast","n":"2","analyte":"silymarin (SMR)","matrix":"plasma","parameter":"AUC","detail":"AUC0-12","value":"11.385","variance":"","units":"µg h ml−1","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 footnotes: 'Average of two measurements'; 'Mean value of two subjects'. No variance given. Units copied as printed (mg symbols as µ)."},{"pmid":"21315924","species":"human","arm":"","form":"Seralon-E capsule (120 mg SMR + 40 mg vitamin E) (Seralon-E capsules (Tiba Pharmaceuticals, Egypt))","forms":[],"dose":"120 mg","doseBasis":"NR","fed":"overnight fast","n":"2","analyte":"silymarin (SMR)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"11.002","variance":"","units":"µg h ml−1","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 footnotes: 'Average of two measurements'; 'Mean value of two subjects'. No variance given. Units copied as printed (mg symbols as µ)."},{"pmid":"21315924","species":"human","arm":"","form":"Seralon-E capsule (120 mg SMR + 40 mg vitamin E) (Seralon-E capsules (Tiba Pharmaceuticals, Egypt))","forms":[],"dose":"120 mg","doseBasis":"NR","fed":"overnight fast","n":"2","analyte":"silymarin (SMR)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"12.985","variance":"","units":"µg h ml−1","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 footnotes: 'Average of two measurements'; 'Mean value of two subjects'. No variance given. 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n not stated; negative CI bounds as printed"},{"pmid":"21865319","species":"human","arm":"","form":"Legalon silymarin hard capsules (140 mg silymarin per capsule per manufacturer; 180 mg milk thistle extract) (Legalon (Rottapharm|Madaus))","forms":["silymarin"],"dose":"560 mg","doseBasis":"active compound","fed":"dosed 30 min after breakfast in subjects fasted overnight","n":"6","analyte":"silychristin conjugates","matrix":"plasma","parameter":"Cmax","detail":"","value":"663","variance":"","units":"ng/ml","location":"Results p.2186","quote":"The steady-state pharmacokinetics of silychristin ... were characterized by a Cmax of 67 ng/ml (−2.5 to 174)","quoteCheck":"value not in quote","note":"Geometric mean and 95% CI per text; n not stated; negative CI bounds as printed"},{"pmid":"21865319","species":"human","arm":"","form":"Legalon silymarin hard capsules (140 mg silymarin per capsule per manufacturer; 180 mg milk thistle extract) (Legalon (Rottapharm|Madaus))","forms":["silymarin"],"dose":"560 mg","doseBasis":"active compound","fed":"dosed 30 min after breakfast in subjects fasted overnight","n":"6","analyte":"silychristin conjugates","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h","value":"3800","variance":"","units":"ng·h/ml","location":"Results p.2186","quote":"The steady-state pharmacokinetics of silychristin ... were characterized by a Cmax of 67 ng/ml (−2.5 to 174)","quoteCheck":"value not in quote","note":"Geometric mean and 95% CI per text; n not stated; negative CI bounds as printed"},{"pmid":"23072776","species":"human","arm":"","form":"water-soluble milk thistle formulation (Sofar), 8 g powder (2 bags) in 400 ml water (Sofar)","forms":["enhanced"],"dose":"8 g formulation equivalent to 380 mg silymarin extract (two bags contained total flavonolignans 484.5 ± 51.3 µmol, n = 5)","doseBasis":"active compound","fed":"overnight fast","n":"14","analyte":"silymarin monoglucuronides","matrix":"urine","parameter":"Tmax","detail":"time of peak urinary excretion","value":"2","variance":"","units":"h","location":"Abstract; Results p.44","quote":"The excretion of monoglucuronides peaked 2 h after consumption","quoteCheck":"supported","note":""},{"pmid":"23072776","species":"human","arm":"","form":"water-soluble milk thistle formulation (Sofar), 8 g powder (2 bags) in 400 ml water (Sofar)","forms":["enhanced"],"dose":"8 g formulation equivalent to 380 mg silymarin extract (two bags contained total flavonolignans 484.5 ± 51.3 µmol, n = 5)","doseBasis":"active compound","fed":"overnight fast","n":"14","analyte":"silymarin sulphate-glucuronides","matrix":"urine","parameter":"Tmax","detail":"time of peak urinary excretion","value":"8","variance":"","units":"h","location":"Abstract; Results p.44","quote":"sulphate–glucuronide and diglucuronide excretion peaked at 8 h","quoteCheck":"supported","note":""},{"pmid":"23072776","species":"human","arm":"","form":"water-soluble milk thistle formulation (Sofar), 8 g powder (2 bags) in 400 ml water (Sofar)","forms":["enhanced"],"dose":"8 g formulation equivalent to 380 mg silymarin extract (two bags contained total flavonolignans 484.5 ± 51.3 µmol, n = 5)","doseBasis":"active compound","fed":"overnight fast","n":"14","analyte":"silymarin diglucuronides","matrix":"urine","parameter":"Tmax","detail":"time of peak urinary excretion","value":"8","variance":"","units":"h","location":"Abstract; Results p.44","quote":"sulphate–glucuronide and diglucuronide excretion peaked at 8 h","quoteCheck":"supported","note":""},{"pmid":"23072776","species":"human","arm":"","form":"water-soluble milk thistle formulation (Sofar), 8 g powder (2 bags) in 400 ml water (Sofar)","forms":["enhanced"],"dose":"8 g formulation equivalent to 380 mg silymarin extract (two bags contained total flavonolignans 484.5 ± 51.3 µmol, n = 5)","doseBasis":"active compound","fed":"overnight fast","n":"14","analyte":"unmetabolised silybin diastereomers","matrix":"urine","parameter":"Tmax","detail":"time of peak urinary excretion","value":"15","variance":"","units":"h","location":"Results p.44","quote":"Unmetabolised silybin and isosilybin diastereomers had a different excretion profile, peaking at 15 and 24 h","quoteCheck":"supported","note":"Sentence lists 'silybin and isosilybin diastereomers ... peaking at 15 and 24 h, respectively'; mapping of 15 h to silybin and 24 h to isosilybin follows the sentence order"},{"pmid":"23072776","species":"human","arm":"","form":"water-soluble milk thistle formulation (Sofar), 8 g powder (2 bags) in 400 ml water (Sofar)","forms":["enhanced"],"dose":"8 g formulation equivalent to 380 mg silymarin extract (two bags contained total flavonolignans 484.5 ± 51.3 µmol, n = 5)","doseBasis":"active compound","fed":"overnight fast","n":"14","analyte":"unmetabolised isosilybin diastereomers","matrix":"urine","parameter":"Tmax","detail":"time of peak urinary excretion","value":"24","variance":"","units":"h","location":"Results p.44","quote":"peaking at 15 and 24 h, respectively","quoteCheck":"supported","note":"Mapping follows sentence order (see silybin row)"},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsule (milk thistle dried extract, 140 mg silymarin per capsule) (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"175 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silybin A","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.5","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"350 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silybin A","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.0","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"525 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silybin A","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.0","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsule (milk thistle dried extract, 140 mg silymarin per capsule) (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"175 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"106.9","variance":"± 49.2 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"350 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"200.5","variance":"± 98.3 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Text prints '200.5 ± 98.' 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extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"91.9","variance":"± 54.0 (SD)","units":"ng×h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"525 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"162.1","variance":"± 72.5 (SD)","units":"ng×h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"350 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silychristin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.5","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"525 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silychristin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.5","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"350 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silychristin","matrix":"plasma","parameter":"Cmax","detail":"","value":"4.6","variance":"± 1.1 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"525 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silychristin","matrix":"plasma","parameter":"Cmax","detail":"","value":"8.5","variance":"± 3.4 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"525 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"32.9","variance":"± 14.3 (SD)","units":"ng×h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"525 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"36.6","variance":"± 14.6 (SD)","units":"ng×h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"525 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silydianin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.5","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"525 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free silydianin","matrix":"plasma","parameter":"Cmax","detail":"","value":"6.4","variance":"± 3.8 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Text (p.1683) prints 6.5 ± 3.8 ng/ml for silydianin; Table 1 prints 6.4 ± 3.8"},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"525 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free taxifolin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.0","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"525 mg extract","doseBasis":"salt/compound","fed":"fasted","n":"13","analyte":"free taxifolin","matrix":"plasma","parameter":"Cmax","detail":"","value":"5.1","variance":"± 2.7 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"175 mg extract","doseBasis":"salt/compound","fed":"NR for steady-state day","n":"13","analyte":"free silybin A","matrix":"plasma","parameter":"Tmax","detail":"steady state","value":"2.0","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"175 mg extract","doseBasis":"salt/compound","fed":"NR for steady-state day","n":"13","analyte":"free silybin A","matrix":"plasma","parameter":"Cmax","detail":"steady state","value":"134.7","variance":"± 72.0 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"175 mg extract","doseBasis":"salt/compound","fed":"NR for steady-state day","n":"13","analyte":"free silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h, steady state","value":"375.6","variance":"± 200.8 (SD)","units":"ng×h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"175 mg extract","doseBasis":"salt/compound","fed":"NR for steady-state day","n":"13","analyte":"free silybin B","matrix":"plasma","parameter":"Tmax","detail":"steady state","value":"1.0","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"175 mg extract","doseBasis":"salt/compound","fed":"NR for steady-state day","n":"13","analyte":"free silybin B","matrix":"plasma","parameter":"Cmax","detail":"steady state","value":"42.1","variance":"± 27.3 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"175 mg extract","doseBasis":"salt/compound","fed":"NR for steady-state day","n":"13","analyte":"free silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h, steady state","value":"99.7","variance":"± 61.8 (SD)","units":"ng×h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"175 mg extract","doseBasis":"salt/compound","fed":"NR for steady-state day","n":"13","analyte":"free isosilybin B","matrix":"plasma","parameter":"Tmax","detail":"steady state","value":"2.0","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Text (p.1683) states median Tmax values were 2, 1, and 1 h for silybin A, silybin B and isosilybin B (isosilybin B 1 h); Table 2 prints 2.0"},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"175 mg extract","doseBasis":"salt/compound","fed":"NR for steady-state day","n":"13","analyte":"free isosilybin B","matrix":"plasma","parameter":"Cmax","detail":"steady state","value":"26.8","variance":"± 19.9 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"23835761","species":"human","arm":"","form":"Legalon 140 capsules (Legalon 140 (MADAUS GmbH))","forms":["silymarin"],"dose":"175 mg extract","doseBasis":"salt/compound","fed":"NR for steady-state day","n":"13","analyte":"free isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h, steady state","value":"66.8","variance":"± 48.4 (SD)","units":"ng×h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"24317417","species":"human","arm":"","form":"silibinin hemisuccinate (IV) (Legalon SIL (Rottapharm|Madaus))","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.4","variance":"± 0.1 (SD)","units":"µg/mL","location":"Results 3.3 p.7","quote":"Cmax (µg/mL): 0.4 ± 0.1 (silibinin A); 0.05 ± 0.02 (silibinin B); 55.0 ± 7.9 (silibinin hemisuccinate A); 28.3 ± 3.9 (silibinin hemisuccinate B).","quoteCheck":"supported","note":"Mean ± SD as stated in text (variance described as inter-subject SD); IV infusion 20 mg/kg expressed as silibinin"},{"pmid":"24317417","species":"human","arm":"","form":"silibinin hemisuccinate (IV) (Legalon SIL (Rottapharm|Madaus))","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.05","variance":"± 0.02 (SD)","units":"µg/mL","location":"Results 3.3 p.7","quote":"Cmax (µg/mL): 0.4 ± 0.1 (silibinin A); 0.05 ± 0.02 (silibinin B); 55.0 ± 7.9 (silibinin hemisuccinate A); 28.3 ± 3.9 (silibinin hemisuccinate B).","quoteCheck":"supported","note":"Mean ± SD as stated in text (variance described as inter-subject SD); IV infusion 20 mg/kg expressed as silibinin"},{"pmid":"24317417","species":"human","arm":"","form":"silibinin hemisuccinate (IV) (Legalon SIL (Rottapharm|Madaus))","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin hemisuccinate A","matrix":"plasma","parameter":"Cmax","detail":"","value":"55.0","variance":"± 7.9 (SD)","units":"µg/mL","location":"Results 3.3 p.7","quote":"Cmax (µg/mL): 0.4 ± 0.1 (silibinin A); 0.05 ± 0.02 (silibinin B); 55.0 ± 7.9 (silibinin hemisuccinate A); 28.3 ± 3.9 (silibinin hemisuccinate B).","quoteCheck":"supported","note":"Mean ± SD as stated in text (variance described as inter-subject SD); IV infusion 20 mg/kg expressed as silibinin"},{"pmid":"24317417","species":"human","arm":"","form":"silibinin hemisuccinate (IV) (Legalon SIL (Rottapharm|Madaus))","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin hemisuccinate B","matrix":"plasma","parameter":"Cmax","detail":"","value":"28.3","variance":"± 3.9 (SD)","units":"µg/mL","location":"Results 3.3 p.7","quote":"Cmax (µg/mL): 0.4 ± 0.1 (silibinin A); 0.05 ± 0.02 (silibinin B); 55.0 ± 7.9 (silibinin hemisuccinate A); 28.3 ± 3.9 (silibinin hemisuccinate B).","quoteCheck":"supported","note":"Mean ± SD as stated in text (variance described as inter-subject SD); IV infusion 20 mg/kg expressed as silibinin"},{"pmid":"24317417","species":"human","arm":"","form":"silibinin hemisuccinate (IV) (Legalon SIL (Rottapharm|Madaus))","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin A","matrix":"plasma","parameter":"AUC","detail":"AUCt (time 0 to last time point, linear trapezoidal)","value":"2.1","variance":"± 0.8 (SD)","units":"µg/mL h","location":"Results 3.3 p.7","quote":"AUCt (µg/mL h): 2.1 ± 0.8 (silibinin A); 0.3 ± 0.1 (silibinin B); 210.7 ± 42.5 (silibinin hemisuccinate A); 86.2 ± 14.6 (silibinin hemisuccinate B).","quoteCheck":"supported","note":"Units printed as µg/mL h; IV infusion"},{"pmid":"24317417","species":"human","arm":"","form":"silibinin hemisuccinate (IV) (Legalon SIL (Rottapharm|Madaus))","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin B","matrix":"plasma","parameter":"AUC","detail":"AUCt (time 0 to last time point, linear trapezoidal)","value":"0.3","variance":"± 0.1 (SD)","units":"µg/mL h","location":"Results 3.3 p.7","quote":"AUCt (µg/mL h): 2.1 ± 0.8 (silibinin A); 0.3 ± 0.1 (silibinin B); 210.7 ± 42.5 (silibinin hemisuccinate A); 86.2 ± 14.6 (silibinin hemisuccinate B).","quoteCheck":"supported","note":"Units printed as µg/mL h; IV infusion"},{"pmid":"24317417","species":"human","arm":"","form":"silibinin hemisuccinate (IV) (Legalon SIL (Rottapharm|Madaus))","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin hemisuccinate A","matrix":"plasma","parameter":"AUC","detail":"AUCt (time 0 to last time point, linear trapezoidal)","value":"210.7","variance":"± 42.5 (SD)","units":"µg/mL h","location":"Results 3.3 p.7","quote":"AUCt (µg/mL h): 2.1 ± 0.8 (silibinin A); 0.3 ± 0.1 (silibinin B); 210.7 ± 42.5 (silibinin hemisuccinate A); 86.2 ± 14.6 (silibinin hemisuccinate B).","quoteCheck":"supported","note":"Units printed as µg/mL h; IV infusion"},{"pmid":"24317417","species":"human","arm":"","form":"silibinin hemisuccinate (IV) (Legalon SIL (Rottapharm|Madaus))","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin hemisuccinate B","matrix":"plasma","parameter":"AUC","detail":"AUCt (time 0 to last time point, linear trapezoidal)","value":"86.2","variance":"± 14.6 (SD)","units":"µg/mL h","location":"Results 3.3 p.7","quote":"AUCt (µg/mL h): 2.1 ± 0.8 (silibinin A); 0.3 ± 0.1 (silibinin B); 210.7 ± 42.5 (silibinin hemisuccinate A); 86.2 ± 14.6 (silibinin hemisuccinate B).","quoteCheck":"supported","note":"Units printed as µg/mL h; IV infusion"},{"pmid":"26595166","species":"human","arm":"","form":"Silymarin capsule (Legalon) (Legalon)","forms":["silymarin"],"dose":"140 mg","doseBasis":"NR","fed":"overnight fast","n":"10","analyte":"silibinin (silybin; glucuronide not included)","matrix":"plasma","parameter":"Cmax","detail":"","value":"144.8","variance":"± 60.1 (SD)","units":"ng/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Decimal points printed as mid-dots in the PDF (e.g. 144·8); text layer drops them; values read from page image; verified on page image (manager QA)"},{"pmid":"26595166","species":"human","arm":"","form":"Silymarin capsule (Legalon) (Legalon)","forms":["silymarin"],"dose":"140 mg","doseBasis":"NR","fed":"overnight fast","n":"10","analyte":"silibinin (silybin; glucuronide not included)","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"347.1","variance":"± 133.8 (SD)","units":"ng/mL h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Decimal points printed as mid-dots in the PDF (e.g. 144·8); text layer drops them; values read from page image; unit printed 'ng/mL h'; verified on page image (manager QA)"},{"pmid":"26595166","species":"human","arm":"","form":"Silymarin capsule (Legalon) (Legalon)","forms":["silymarin"],"dose":"140 mg","doseBasis":"NR","fed":"overnight fast","n":"10","analyte":"silibinin (silybin; glucuronide not included)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.7","variance":"± 0.5 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Decimal points printed as mid-dots in the PDF (e.g. 144·8); text layer drops them; values read from page image; tmax analysed by Kruskal-Wallis but reported as mean ± SD; verified on page image (manager QA)"},{"pmid":"26595166","species":"human","arm":"","form":"Silymarin capsule (Legalon) (Legalon)","forms":["silymarin"],"dose":"140 mg","doseBasis":"NR","fed":"overnight fast","n":"8","analyte":"silibinin (silybin; glucuronide not included)","matrix":"plasma","parameter":"Cmax","detail":"","value":"129.3","variance":"± 50.3 (SD)","units":"ng/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Decimal points printed as mid-dots in the PDF (e.g. 144·8); text layer drops them; values read from page image; verified on page image (manager QA)"},{"pmid":"26595166","species":"human","arm":"","form":"Silymarin capsule (Legalon) (Legalon)","forms":["silymarin"],"dose":"140 mg","doseBasis":"NR","fed":"overnight fast","n":"8","analyte":"silibinin (silybin; glucuronide not included)","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"312.7","variance":"± 145.4 (SD)","units":"ng/mL h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Decimal points printed as mid-dots in the PDF (e.g. 144·8); text layer drops them; values read from page image; unit printed 'ng/mL h'; verified on page image (manager QA)"},{"pmid":"26595166","species":"human","arm":"","form":"Silymarin capsule (Legalon) (Legalon)","forms":["silymarin"],"dose":"140 mg","doseBasis":"NR","fed":"overnight fast","n":"8","analyte":"silibinin (silybin; glucuronide not included)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.9","variance":"± 0.6 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Decimal points printed as mid-dots in the PDF (e.g. 144·8); text layer drops them; values read from page image; tmax analysed by Kruskal-Wallis but reported as mean ± SD; verified on page image (manager QA)"},{"pmid":"26595166","species":"human","arm":"","form":"Silymarin capsule (Legalon) (Legalon)","forms":["silymarin"],"dose":"140 mg","doseBasis":"NR","fed":"overnight fast","n":"5","analyte":"silibinin (silybin; glucuronide not included)","matrix":"plasma","parameter":"Cmax","detail":"","value":"60.1","variance":"± 18.3 (SD)","units":"ng/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Decimal points printed as mid-dots in the PDF (e.g. 144·8); text layer drops them; values read from page image; verified on page image (manager QA)"},{"pmid":"26595166","species":"human","arm":"","form":"Silymarin capsule (Legalon) (Legalon)","forms":["silymarin"],"dose":"140 mg","doseBasis":"NR","fed":"overnight fast","n":"5","analyte":"silibinin (silybin; glucuronide not included)","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"228.3","variance":"± 52.9 (SD)","units":"ng/mL h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Decimal points printed as mid-dots in the PDF (e.g. 144·8); text layer drops them; values read from page image; unit printed 'ng/mL h'; verified on page image (manager QA)"},{"pmid":"26595166","species":"human","arm":"","form":"Silymarin capsule (Legalon) (Legalon)","forms":["silymarin"],"dose":"140 mg","doseBasis":"NR","fed":"overnight fast","n":"5","analyte":"silibinin (silybin; glucuronide not included)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.8","variance":"± 0.6 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Decimal points printed as mid-dots in the PDF (e.g. 144·8); text layer drops them; values read from page image; tmax analysed by Kruskal-Wallis but reported as mean ± SD; verified on page image (manager QA)"},{"pmid":"26642669","species":"human","arm":"","form":"Silymarin 200 mg tablet (Abbott Pharmaceuticals Pvt. Ltd., Karachi (brand name NR))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"Fasted after midnight, dosed 9:00 a.m., fasted 3 h post-dose","n":"8","analyte":"silymarin (silychristin, silydianin, silybin A and B; total after glucuronidase hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"2.79","variance":"± 0.35 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26642669","species":"human","arm":"","form":"Silymarin 200 mg tablet (Abbott Pharmaceuticals Pvt. Ltd., Karachi (brand name NR))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"Fasted after midnight, dosed 9:00 a.m., fasted 3 h post-dose","n":"8","analyte":"silymarin (silychristin, silydianin, silybin A and B; total after glucuronidase hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.86","variance":"± 0.12 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"female vs male, unpaired t test: p printed in Table 3"},{"pmid":"26642669","species":"human","arm":"","form":"Silymarin 200 mg tablet (Abbott Pharmaceuticals Pvt. Ltd., Karachi (brand name NR))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"Fasted after midnight, dosed 9:00 a.m., fasted 3 h post-dose","n":"8","analyte":"silymarin (silychristin, silydianin, silybin A and B; total after glucuronidase hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.14","variance":"± 0.26 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 prints no unit for Tmax; unit h from Table 4"},{"pmid":"26642669","species":"human","arm":"","form":"Silymarin 200 mg tablet (Abbott Pharmaceuticals Pvt. Ltd., Karachi (brand name NR))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"Fasted after midnight, dosed 9:00 a.m., fasted 3 h post-dose","n":"8","analyte":"silymarin (silychristin, silydianin, silybin A and B; total after glucuronidase hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.6","variance":"± 0.12 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 prints no unit for Tmax; unit h from Table 4; female vs male, unpaired t test: p printed in Table 3"},{"pmid":"26642669","species":"human","arm":"","form":"Silymarin 200 mg tablet (Abbott Pharmaceuticals Pvt. Ltd., Karachi (brand name NR))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"Fasted after midnight, dosed 9:00 a.m., fasted 3 h post-dose","n":"8","analyte":"silymarin (silychristin, silydianin, silybin A and B; total after glucuronidase hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC (model-derived; interval not stated)","value":"12.82","variance":"± 0.77 (SD)","units":"µg×h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"unit printed in the row label (verified on page image)"},{"pmid":"26642669","species":"human","arm":"","form":"Silymarin 200 mg tablet (Abbott Pharmaceuticals Pvt. Ltd., Karachi (brand name NR))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"Fasted after midnight, dosed 9:00 a.m., fasted 3 h post-dose","n":"8","analyte":"silymarin (silychristin, silydianin, silybin A and B; total after glucuronidase hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC (model-derived; interval not stated)","value":"11.27","variance":"± 1.01 (SD)","units":"µg×h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"female vs male, unpaired t test: p printed in Table 3; unit printed in the row label (verified on page image)"},{"pmid":"26642669","species":"human","arm":"","form":"Silymarin 200 mg tablet (Abbott Pharmaceuticals Pvt. Ltd., Karachi (brand name NR))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"Fasted after midnight, dosed 9:00 a.m., fasted 3 h post-dose","n":"8","analyte":"silymarin (silychristin, silydianin, silybin A and B; total after glucuronidase hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC polyexponential (t = 12)","value":"12.79","variance":"± 0.75 (SD)","units":"NR","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Unit not printed on this row of Table 3 (only the first AUC row label has µg×h/mL); not assumed."},{"pmid":"26642669","species":"human","arm":"","form":"Silymarin 200 mg tablet (Abbott Pharmaceuticals Pvt. Ltd., Karachi (brand name NR))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"Fasted after midnight, dosed 9:00 a.m., fasted 3 h post-dose","n":"8","analyte":"silymarin (silychristin, silydianin, silybin A and B; total after glucuronidase hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC polyexponential (t = 12)","value":"11.21","variance":"± 0.99 (SD)","units":"NR","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Unit not printed on this row of Table 3 (only the first AUC row label has µg×h/mL); not assumed. female vs male, unpaired t test: p printed in Table 3"},{"pmid":"26642669","species":"human","arm":"","form":"Silymarin 200 mg tablet (Abbott Pharmaceuticals Pvt. 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(ref 16) shown for comparison; not measured in this study; not gender-specific"},{"pmid":"26642669","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silymarin (Usman et al. study; product Silliver)","matrix":"plasma","parameter":"AUC","detail":"Silliver (Usman et al., published work, 200 mg), literature comparison","value":"10.8","variance":"","units":"µg×h/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Literature values from Usman et al. (ref 16) shown for comparison; not measured in this study; not gender-specific"},{"pmid":"26642669","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silymarin (Usman et al. study; product Silimarin)","matrix":"plasma","parameter":"AUC","detail":"Silimarin (Usman et al., published work, 200 mg), literature comparison","value":"11.2","variance":"","units":"µg×h/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Literature values from Usman et al. (ref 16) shown for comparison; not measured in this study; not gender-specific"},{"pmid":"28098838","species":"human","arm":"","form":"Legalon silymarin capsules (180 mg milk thistle extract; 23.2 mg silybin A, 32.0 mg silybin B per capsule) (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140, 280, 560 or 700 mg silymarin","doseBasis":"NR","fed":"NR","n":"10","analyte":"silybin A","matrix":"plasma (parent flavonolignan)","parameter":"AUC","detail":"dose-normalized AUC0-48h","value":"0.17","variance":"± 25th, 75th percentile: 0.13, 0.2 (IQR)","units":"ng·h/mL·mg","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Printed as Median (25th, 75th). Dose-normalized: AUC divided by mg dose administered (Methods 3.8)."},{"pmid":"28098838","species":"human","arm":"","form":"Legalon silymarin capsules (Legalon (Madaus Rottapharm))","forms":["silymarin"],"dose":"140, 280, 560 or 700 mg silymarin","doseBasis":"NR","fed":"NR","n":"14","analyte":"silybin A","matrix":"plasma (parent flavonolignan)","parameter":"AUC","detail":"dose-normalized AUC0-48h","value":"0.19","variance":"± 25th, 75th percentile: 0.15, 0.23 (IQR)","units":"ng·h/mL·mg","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Printed as Median (25th, 75th). 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fasted 4 h after dose, then standard lunch (deli sub sandwich, potato chips, 12-oz soda or water)","n":"12","analyte":"silybin B (non-conjugated)","matrix":"plasma","parameter":"AUC","detail":"AUC0-last","value":"110.95","variance":"± 74.26 (SD)","units":"ng · h/mL","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29273470","species":"human","arm":"","form":"2 soft gels, 160 mg milk thistle extract (55% silymarin) per soft gel, multi-ingredient dietary supplement incl. flaxseed oil and phosphatidylcholine (IsaGenesis (Isagenix International))","forms":[],"dose":"2 capsules (one serving) capsules","doseBasis":"NR","fed":"overnight fast; fasted 4 h after dose, then standard lunch (deli sub sandwich, potato chips, 12-oz soda or water)","n":"12","analyte":"silybin B (non-conjugated)","matrix":"plasma","parameter":"AUC","detail":"AUC0-last per dose","value":"1.27","variance":"± 0.85 (SD)","units":"ng · h/mL/mg","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29273470","species":"human","arm":"","form":"2 soft gels, 160 mg milk thistle extract (55% silymarin) per soft gel, multi-ingredient dietary supplement incl. flaxseed oil and phosphatidylcholine (IsaGenesis (Isagenix International))","forms":[],"dose":"2 capsules (one serving) capsules","doseBasis":"NR","fed":"overnight fast; fasted 4 h after dose, then standard lunch (deli sub sandwich, potato chips, 12-oz soda or water)","n":"12","analyte":"silybin B (non-conjugated)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf per dose","value":"1.31","variance":"± 0.84 (SD)","units":"ng · h/mL/mg","location":"Table III","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29273470","species":"human","arm":"","form":"2 soft gels, 160 mg milk thistle extract (55% silymarin) per soft gel, multi-ingredient dietary supplement incl. flaxseed oil and phosphatidylcholine (IsaGenesis (Isagenix International))","forms":[],"dose":"2 capsules (one serving) capsules","doseBasis":"NR","fed":"overnight fast; fasted 4 h after dose, then standard lunch (deli sub sandwich, potato chips, 12-oz soda or water)","n":"12","analyte":"silybin A (non-conjugated)","matrix":"plasma","parameter":"relative_bioavailability","detail":"F % IsaGenesis/Product B (dose-corrected AUC0-last)","value":"284","variance":"","units":"%","location":"Table III","quote":"284% (silybin A) and 334% (silybin B) greater than with the Product B formulation","quoteCheck":"supported","note":"Text phrase 'greater than' while the printed value is the ratio; Table III footnote: relative bioavailability of IsaGenesis compared with Product B"},{"pmid":"29273470","species":"human","arm":"","form":"2 soft gels, 160 mg milk thistle extract (55% silymarin) per soft gel, multi-ingredient dietary supplement incl. flaxseed oil and phosphatidylcholine (IsaGenesis (Isagenix International))","forms":[],"dose":"2 capsules (one serving) capsules","doseBasis":"NR","fed":"overnight fast; fasted 4 h after dose, then standard lunch (deli sub sandwich, potato chips, 12-oz soda or water)","n":"12","analyte":"silybin B (non-conjugated)","matrix":"plasma","parameter":"relative_bioavailability","detail":"F % IsaGenesis/Product B (dose-corrected AUC0-last)","value":"334","variance":"","units":"%","location":"Table III","quote":"284% (silybin A) and 334% (silybin B) greater than with the Product B formulation","quoteCheck":"supported","note":"Text phrase 'greater than' while the printed value is the ratio"},{"pmid":"30108644","species":"human","arm":"","form":"Silyvercell Soft Capsules (SMEDDS) containing 175 mg Carduus marianus extract (Silyvercell (Phil Inter Pharma, Vietnam))","forms":["enhanced"],"dose":"140 mg silymarin (one capsule; calculated as 60 mg silybin)","doseBasis":"active compound","fed":"fasted","n":"12","analyte":"plasma silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"812.43","variance":"± 434.07 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Range upper limit 1505.49 in Table 2 vs 1505.47 in Abstract/Results 3.1/Conclusions (inconsistent)"},{"pmid":"30108644","species":"human","arm":"","form":"Silyvercell Soft Capsules (SMEDDS) containing 175 mg Carduus marianus extract (Silyvercell (Phil Inter Pharma, Vietnam))","forms":["enhanced"],"dose":"140 mg silymarin (one capsule; calculated as 60 mg silybin)","doseBasis":"active compound","fed":"fasted","n":"12","analyte":"plasma silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"658.80","variance":"± 266.23 (SD)","units":"ng.h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Arithmetic mean ± SD per Table 2"},{"pmid":"30108644","species":"human","arm":"","form":"Silyvercell Soft Capsules (SMEDDS) containing 175 mg Carduus marianus extract (Silyvercell (Phil Inter Pharma, Vietnam))","forms":["enhanced"],"dose":"140 mg silymarin (one capsule; calculated as 60 mg silybin)","doseBasis":"active compound","fed":"fasted","n":"12","analyte":"plasma silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"676.98","variance":"± 268.34 (SD)","units":"ng.h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Arithmetic mean ± SD per Table 2"},{"pmid":"30108644","species":"human","arm":"","form":"Silyvercell Soft Capsules (SMEDDS) containing 175 mg Carduus marianus extract (Silyvercell (Phil Inter Pharma, Vietnam))","forms":["enhanced"],"dose":"140 mg silymarin (one capsule; calculated as 60 mg silybin)","doseBasis":"active compound","fed":"fasted","n":"12","analyte":"plasma silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.80","variance":"± 0.44 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Arithmetic mean ± SD per Table 2"},{"pmid":"30108644","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"plasma silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.54","variance":"± 0.19 (SD)","units":"h","location":"Results 3.1 (p.4)","quote":"tmax (0.54 ± 0.19 versus 1.06 ± 0.48 h) (p<0.05)","quoteCheck":"supported","note":"Sex subgroup; n=6 males stated in Results 3.1"},{"pmid":"30108644","species":"human","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"plasma silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.06","variance":"± 0.48 (SD)","units":"h","location":"Results 3.1 (p.4)","quote":"tmax (0.54 ± 0.19 versus 1.06 ± 0.48 h) (p<0.05)","quoteCheck":"supported","note":"Sex subgroup; n=6 females stated in Results 3.1"},{"pmid":"30635055","species":"human","arm":"","form":"SPC in oily-medium soft-gel capsules (NeoCholal-S (Laboratorios Italmex))","forms":["phytosome"],"dose":"45 mg SPC","doseBasis":"salt/compound","fed":"fasted","n":"23","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.1","variance":"± 0.7 (SE)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table caption/header says 'Mean ± SE'; P compares formulations"},{"pmid":"30635055","species":"human","arm":"","form":"silymarin tablet (Legalon 70 mg (Laboratorios Takeda))","forms":["silymarin"],"dose":"70 mg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"23","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.9","variance":"± 0.9 (SE)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table caption/header says 'Mean ± SE'; P compares formulations"},{"pmid":"30635055","species":"human","arm":"","form":"SPC in oily-medium soft-gel capsules (NeoCholal-S (Laboratorios Italmex))","forms":["phytosome"],"dose":"45 mg SPC","doseBasis":"salt/compound","fed":"fasted","n":"23","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"207.1","variance":"± 62.4 (SE)","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table caption/header says 'Mean ± SE'; P compares formulations"},{"pmid":"30635055","species":"human","arm":"","form":"silymarin tablet (Legalon 70 mg (Laboratorios Takeda))","forms":["silymarin"],"dose":"70 mg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"23","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"12.6","variance":"± 31.4 (SE)","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table caption/header says 'Mean ± SE'; P compares formulations"},{"pmid":"30635055","species":"human","arm":"","form":"SPC in oily-medium soft-gel capsules (NeoCholal-S (Laboratorios Italmex))","forms":["phytosome"],"dose":"45 mg SPC","doseBasis":"salt/compound","fed":"fasted","n":"23","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-T","value":"302.6","variance":"± 126.6 (SE)","units":"ng/h/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table caption/header says 'Mean ± SE'; P compares formulations"},{"pmid":"30635055","species":"human","arm":"","form":"silymarin tablet (Legalon 70 mg (Laboratorios Takeda))","forms":["silymarin"],"dose":"70 mg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"23","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-T","value":"26.4","variance":"± 56.7 (SE)","units":"ng/h/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table caption/header says 'Mean ± SE'; P compares formulations"},{"pmid":"30635055","species":"human","arm":"","form":"SPC in oily-medium soft-gel capsules (NeoCholal-S (Laboratorios Italmex))","forms":["phytosome"],"dose":"45 mg SPC","doseBasis":"salt/compound","fed":"fasted","n":"23","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"308.8","variance":"± 126.1 (SE)","units":"ng/h/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table caption/header says 'Mean ± SE'; P compares formulations"},{"pmid":"30635055","species":"human","arm":"","form":"silymarin tablet (Legalon 70 mg (Laboratorios Takeda))","forms":["silymarin"],"dose":"70 mg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"23","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"29.5","variance":"± 14.1 (SE)","units":"ng/h/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table caption/header says 'Mean ± SE'; P compares formulations"},{"pmid":"30635055","species":"human","arm":"","form":"SPC in oily-medium soft-gel capsules (NeoCholal-S (Laboratorios Italmex))","forms":["phytosome"],"dose":"45 mg SPC","doseBasis":"salt/compound","fed":"fasted","n":"23","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"Cmax as printed in Results text","value":"207.1","variance":"","units":"mg/L","location":"Results p.3","quote":"SIB peak plasma concentrations were 207.1 mg/L for SPC and 12.6 mg/L for SM tablets.","quoteCheck":"supported","note":"Units printed as mg/L in text vs ng/mL in Table 1 (inconsistent)"},{"pmid":"30635055","species":"human","arm":"","form":"silymarin tablet (Legalon 70 mg (Laboratorios Takeda))","forms":["silymarin"],"dose":"70 mg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"23","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"Cmax as printed in Results text","value":"12.6","variance":"","units":"mg/L","location":"Results p.3","quote":"SIB peak plasma concentrations were 207.1 mg/L for SPC and 12.6 mg/L for SM tablets.","quoteCheck":"supported","note":"Units printed as mg/L in text vs ng/mL in Table 1 (inconsistent)"},{"pmid":"30635055","species":"human","arm":"","form":"SPC in oily-medium soft-gel capsules (NeoCholal-S (Laboratorios Italmex))","forms":["phytosome"],"dose":"45 mg SPC","doseBasis":"salt/compound","fed":"fasted","n":"23","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"SPC capsule vs SM tablet (Discussion)","value":"9.6","variance":"","units":"times","location":"Discussion p.4","quote":"SIB bioavailability is 9.6 times higher with SPC in oily-medium soft-gel capsules compared with conventional SM tablets","quoteCheck":"supported","note":"Basis (AUC/Cmax, dose-normalised or not) not stated; Methods mention 90% CI of Cmax and AUC0-inf ratios but numeric ratios/CIs are not printed"},{"pmid":"35061161","species":"human","arm":"","form":"silybin A tablet (80% release in 45 min as model input)","forms":[],"dose":"140 mg","doseBasis":"active compound","fed":"NR","n":"1 (virtual individual)","analyte":"silybin A","matrix":"plasma (simulated)","parameter":"AUC","detail":"AUC0-24","value":"4.35","variance":"","units":"µmol.h/l","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"silybin A tablet (80% release in 45 min as model input)","forms":[],"dose":"140 mg","doseBasis":"active compound","fed":"NR","n":"1 (virtual individual)","analyte":"silybin A","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"0.32","variance":"","units":"µmol/l","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"silybin A tablet (80% release in 45 min as model input)","forms":[],"dose":"140 mg","doseBasis":"active compound","fed":"NR","n":"1 (virtual individual)","analyte":"silybin A","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"3.2","variance":"","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"silybin A tablet","forms":[],"dose":"140 mg","doseBasis":"active compound","fed":"NR","n":"96","analyte":"silybin A","matrix":"plasma (simulated)","parameter":"AUC","detail":"AUC0-24","value":"2.53","variance":"","units":"µmol.h/l","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"silybin A tablet","forms":[],"dose":"140 mg","doseBasis":"active compound","fed":"NR","n":"96","analyte":"silybin A","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"0.51","variance":"","units":"µmol/l","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement; text (Results p.5) gives population Cmax as 0.5"},{"pmid":"35061161","species":"human","arm":"","form":"silybin A tablet","forms":[],"dose":"140 mg","doseBasis":"active compound","fed":"NR","n":"96","analyte":"silybin A","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"2.75","variance":"","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"NR","forms":[],"dose":"140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"silybin A","matrix":"plasma (simulated)","parameter":"AUC","detail":"AUC0-24","value":"5.92","variance":"","units":"µmol.h/l","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study (ref [4] Brantley 2014), as listed in Table 4"},{"pmid":"35061161","species":"human","arm":"","form":"NR","forms":[],"dose":"140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"silybin A","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"0.38","variance":"","units":"µmol/l","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study (ref [4] Brantley 2014), as listed in Table 4"},{"pmid":"35061161","species":"human","arm":"","form":"NR","forms":[],"dose":"140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"silybin A","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"3.6","variance":"","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study (ref [4] Brantley 2014), as listed in Table 4"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"1 (virtual)","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"AUC0-24","value":"1082","variance":"","units":"ng.h/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"1 (virtual)","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"1.1","variance":"","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"1 (virtual)","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"32.9","variance":"","units":"ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"12","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"AUC0-24","value":"1125.65","variance":"","units":"ng.h/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"12","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"1.5","variance":"","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"12","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"289","variance":"","units":"ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"AUC0-24","value":"808 ± 193","variance":"± 193 (NR)","units":"ng.h/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study ([21] Chinese / [47] Korean), as listed in Table 4; variance type not stated ('±')"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"1.1 ± 0.71","variance":"± 0.71 (NR)","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study ([21] Chinese / [47] Korean), as listed in Table 4; variance type not stated ('±')"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"262 ± 81","variance":"± 81 (NR)","units":"ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study ([21] Chinese / [47] Korean), as listed in Table 4; variance type not stated ('±')"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"1 (virtual)","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"AUC0-24","value":"1199.86","variance":"","units":"ng.h/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"1 (virtual)","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"2.46","variance":"","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"1 (virtual)","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"440.76","variance":"","units":"ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"100","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"AUC0-24","value":"1531","variance":"","units":"ng.h/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"100","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"2.8","variance":"","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"100","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"302","variance":"","units":"ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"AUC0-24","value":"1334.9","variance":"","units":"ng.h/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study ([21] Chinese / [47] Korean), as listed in Table 4"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"NR","variance":"","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study ([21] Chinese / [47] Korean), as listed in Table 4; Table prints 'Not given'"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"440.2","variance":"","units":"ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study ([21] Chinese / [47] Korean), as listed in Table 4"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"","value":"854.3 ± 236.9","variance":"± 236.9 (NR)","units":"ng.h/ml","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study (ref [8] Han 2009) in CYP2C9*1/*1 genotype; variance type not stated ('±')"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"323.3 ± 121.0","variance":"± 121.0 (NR)","units":"ng/ml","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study (ref [8] Han 2009) in CYP2C9*1/*1 genotype; variance type not stated ('±')"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"1.86 ± 0.80","variance":"± 0.80 (NR)","units":"ng/ml","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study (ref [8] Han 2009) in CYP2C9*1/*1 genotype; variance type not stated ('±'); Table prints Tmax unit as 'ng/ml' (apparent labelling error; text uses h)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"","value":"816.3 ± 282.9","variance":"± 282.9 (NR)","units":"ng.h/ml","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study (ref [8] Han 2009) in CYP2C9*1/*3 genotype; variance type not stated ('±')"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"260.8 ± 150.4","variance":"± 150.4 (NR)","units":"ng/ml","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study (ref [8] Han 2009) in CYP2C9*1/*3 genotype; variance type not stated ('±')"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"1.93 ± 0.75","variance":"± 0.75 (NR)","units":"ng/ml","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Observed value from cited clinical study (ref [8] Han 2009) in CYP2C9*1/*3 genotype; variance type not stated ('±'); Table prints Tmax unit as 'ng/ml' (apparent labelling error; text uses h)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"","value":"1051.42","variance":"","units":"ng.h/ml","location":"Table 5/6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan alone, CYP2C9*1/*1)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan + silybin A","forms":[],"dose":"50 / 140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"","value":"1220","variance":"","units":"ng.h/ml","location":"Table 6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan + silybin A 420 mg/day, CYP2C9*1/*1)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"250.88","variance":"","units":"ng/ml","location":"Table 5/6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan alone, CYP2C9*1/*1)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan + silybin A","forms":[],"dose":"50 / 140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"346.07","variance":"","units":"ng/ml","location":"Table 6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan + silybin A 420 mg/day, CYP2C9*1/*1)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"2.30","variance":"","units":"ng/ml","location":"Table 5/6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan alone, CYP2C9*1/*1); Table 5/6 prints Tmax unit as 'ng/ml' (apparent labelling error; text uses h)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan + silybin A","forms":[],"dose":"50 / 140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"1.65","variance":"","units":"ng/ml","location":"Table 6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan + silybin A 420 mg/day, CYP2C9*1/*1); Table 5/6 prints Tmax unit as 'ng/ml' (apparent labelling error; text uses h)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"","value":"1211.85","variance":"","units":"ng.h/ml","location":"Table 5/6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan alone, CYP2C9*1/*2)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan + silybin A","forms":[],"dose":"50 / 140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"","value":"22.57","variance":"","units":"ng.h/ml","location":"Table 6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan + silybin A 420 mg/day, CYP2C9*1/*2)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"260.79","variance":"","units":"ng/ml","location":"Table 5/6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan alone, CYP2C9*1/*2)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan + silybin A","forms":[],"dose":"50 / 140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"3.15","variance":"","units":"ng/ml","location":"Table 6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan + silybin A 420 mg/day, CYP2C9*1/*2); Results p.5 text prints with-silybin Cmax as 3.14 (Table 6: 3.15)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"2.30","variance":"","units":"ng/ml","location":"Table 5/6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan alone, CYP2C9*1/*2); Table 5/6 prints Tmax unit as 'ng/ml' (apparent labelling error; text uses h)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan + silybin A","forms":[],"dose":"50 / 140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"1.40","variance":"","units":"ng/ml","location":"Table 6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan + silybin A 420 mg/day, CYP2C9*1/*2); Table 5/6 prints Tmax unit as 'ng/ml' (apparent labelling error; text uses h); Results p.5 text prints with-silybin tmax as 1.35 (Table 6: 1.40)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"","value":"768.99","variance":"","units":"ng.h/ml","location":"Table 5/6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan alone, CYP2C9*1/*3)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan + silybin A","forms":[],"dose":"50 / 140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"AUC","detail":"","value":"880.09","variance":"","units":"ng.h/ml","location":"Table 6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan + silybin A 420 mg/day, CYP2C9*1/*3)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"179.57","variance":"","units":"ng/ml","location":"Table 5/6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan alone, CYP2C9*1/*3)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan + silybin A","forms":[],"dose":"50 / 140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Cmax","detail":"","value":"609.85","variance":"","units":"ng/ml","location":"Table 6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan + silybin A 420 mg/day, CYP2C9*1/*3)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan","forms":[],"dose":"50 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"2.40","variance":"","units":"ng/ml","location":"Table 5/6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan alone, CYP2C9*1/*3); Table 5/6 prints Tmax unit as 'ng/ml' (apparent labelling error; text uses h)"},{"pmid":"35061161","species":"human","arm":"","form":"losartan + silybin A","forms":[],"dose":"50 / 140 mg","doseBasis":"NR","fed":"NR","n":"NR","analyte":"losartan","matrix":"plasma (simulated)","parameter":"Tmax","detail":"","value":"0.80","variance":"","units":"ng/ml","location":"Table 6","quote":"","quoteCheck":"no quote","note":"PBPK model prediction (in silico), not a measurement (losartan + silybin A 420 mg/day, CYP2C9*1/*3); Table 5/6 prints Tmax unit as 'ng/ml' (apparent labelling error; text uses h)"},{"pmid":"39204378","species":"human","arm":"","form":"milk thistle raw material (Indena, 38.3 +/- 0.4% w/w silybin) dispersed in 1.0 mL DI water","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.25","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Single value printed, no variance"},{"pmid":"39204378","species":"human","arm":"","form":"milk thistle raw material (Indena, 38.3 +/- 0.4% w/w silybin) dispersed in 1.0 mL DI water","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"703","variance":"± 372 (SD)","units":"ng/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39204378","species":"human","arm":"","form":"milk thistle raw material (Indena, 38.3 +/- 0.4% w/w silybin) dispersed in 1.0 mL DI water","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"1340","variance":"± 488 (SD)","units":"ng·h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39204378","species":"human","arm":"","form":"milk thistle raw material (Indena, 38.3 +/- 0.4% w/w silybin) dispersed in 1.0 mL DI water","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative to milk thistle raw material (AUCinf)","value":"100","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Reference set to 100"},{"pmid":"39204378","species":"human","arm":"","form":"HM40 (milk thistle raw material + xanthan gum + gum ghatti, 1:0.1:0.4 w/w, 26.0% silybin) dispersed in 1.0 mL DI water","forms":["enhanced"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.25","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Single value printed, no variance"},{"pmid":"39204378","species":"human","arm":"","form":"HM40 (milk thistle raw material + xanthan gum + gum ghatti, 1:0.1:0.4 w/w, 26.0% silybin) dispersed in 1.0 mL DI water","forms":["enhanced"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"3320","variance":"± 765 (SD)","units":"ng/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39204378","species":"human","arm":"","form":"HM40 (milk thistle raw material + xanthan gum + gum ghatti, 1:0.1:0.4 w/w, 26.0% silybin) dispersed in 1.0 mL DI water","forms":["enhanced"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"3500","variance":"± 617 (SD)","units":"ng·h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39204378","species":"human","arm":"","form":"HM40 (milk thistle raw material + xanthan gum + gum ghatti, 1:0.1:0.4 w/w, 26.0% silybin) dispersed in 1.0 mL DI water","forms":["enhanced"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative to milk thistle raw material (AUCinf)","value":"262","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Text/Abstract/Conclusions state 2.61-fold higher oral bioavailability (Table prints 262%)"},{"pmid":"39204378","species":"human","arm":"","form":"Enerthistle capsule containing milk thistle raw material","forms":["silymarin"],"dose":"75 mg as silybin","doseBasis":"active compound","fed":"fasted 10 h before and 4 h after dosing; 240 mL water","n":"14","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.98","variance":"± 0.50 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39204378","species":"human","arm":"","form":"Enerthistle capsule containing milk thistle raw material","forms":["silymarin"],"dose":"75 mg as silybin","doseBasis":"active compound","fed":"fasted 10 h before and 4 h after dosing; 240 mL water","n":"14","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"158","variance":"± 52 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39204378","species":"human","arm":"","form":"Enerthistle capsule containing milk thistle raw material","forms":["silymarin"],"dose":"75 mg as silybin","doseBasis":"active compound","fed":"fasted 10 h before and 4 h after dosing; 240 mL water","n":"14","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"209","variance":"± 63 (SD)","units":"ng·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39204378","species":"human","arm":"","form":"Enerthistle capsule containing milk thistle raw material","forms":["silymarin"],"dose":"75 mg as silybin","doseBasis":"active compound","fed":"fasted 10 h before and 4 h after dosing; 240 mL water","n":"14","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative to reference capsule (AUCinf)","value":"100","variance":"","units":"%","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Reference set to 100"},{"pmid":"39204378","species":"human","arm":"","form":"HM40 dispersed in grapeseed oil in soft gelatin capsule","forms":["enhanced"],"dose":"75 mg as silybin","doseBasis":"active compound","fed":"fasted 10 h before and 4 h after dosing; 240 mL water","n":"14","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.03","variance":"± 0.52 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39204378","species":"human","arm":"","form":"HM40 dispersed in grapeseed oil in soft gelatin capsule","forms":["enhanced"],"dose":"75 mg as silybin","doseBasis":"active compound","fed":"fasted 10 h before and 4 h after dosing; 240 mL water","n":"14","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"323","variance":"± 121 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39204378","species":"human","arm":"","form":"HM40 dispersed in grapeseed oil in soft gelatin capsule","forms":["enhanced"],"dose":"75 mg as silybin","doseBasis":"active compound","fed":"fasted 10 h before and 4 h after dosing; 240 mL water","n":"14","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"316","variance":"± 72 (SD)","units":"ng·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39204378","species":"human","arm":"","form":"HM40 dispersed in grapeseed oil in soft gelatin capsule","forms":["enhanced"],"dose":"75 mg as silybin","doseBasis":"active compound","fed":"fasted 10 h before and 4 h after dosing; 240 mL water","n":"14","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative to reference capsule (AUCinf)","value":"151","variance":"","units":"%","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Text states 1.5-fold higher oral bioavailability (Table prints 151%)"},{"pmid":"40733088","species":"human","arm":"","form":"Hard-gelatin capsule, powder (Organika Health Products Milk Thistle, Lot 100284)","forms":["silymarin"],"dose":"130 mg silymarin","doseBasis":"active compound","fed":"standardized breakfast","n":"16","analyte":"total silymarin (free + conjugated, after beta-glucuronidase)","matrix":"capillary whole blood","parameter":"Tmax","detail":"","value":"2.0","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 value; abstract and Results text/Discussion print STD median 2.5 h (range/95% CI 0.5–8.0), inconsistent with Table 3 (2.0, 0.5–6.0)"},{"pmid":"40733088","species":"human","arm":"","form":"Soft-gelatin capsule, liquid; anhydrous self-emulsifying system with MCT and phosphatidylcholine (LipoMicel Milk Thistle, Lot 2001076 (Natural Factors))","forms":["enhanced"],"dose":"130 mg silymarin","doseBasis":"active compound","fed":"standardized breakfast","n":"16","analyte":"total silymarin (free + conjugated, after beta-glucuronidase)","matrix":"capillary whole blood","parameter":"Tmax","detail":"","value":"0.5","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 and abstract agree (0.5; 0.5–4.0)"},{"pmid":"40733088","species":"human","arm":"","form":"Hard-gelatin capsule, powder (Organika Health Products Milk Thistle, Lot 100284)","forms":["silymarin"],"dose":"130 mg silymarin","doseBasis":"active compound","fed":"standardized breakfast","n":"16","analyte":"total silymarin (free + conjugated, after beta-glucuronidase)","matrix":"capillary whole blood","parameter":"Cmax","detail":"arithmetic mean","value":"66.1","variance":"± 114.8 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"40733088","species":"human","arm":"","form":"Hard-gelatin capsule, powder (Organika Health Products Milk Thistle, Lot 100284)","forms":["silymarin"],"dose":"130 mg silymarin","doseBasis":"active compound","fed":"standardized breakfast","n":"16","analyte":"total silymarin (free + conjugated, after beta-glucuronidase)","matrix":"capillary whole blood","parameter":"Cmax","detail":"","value":"7.7","variance":"","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Abstract also prints CI 1.9–30.7 ng/mL"},{"pmid":"40733088","species":"human","arm":"","form":"Soft-gelatin capsule, liquid; anhydrous self-emulsifying system with MCT and phosphatidylcholine (LipoMicel Milk Thistle, Lot 2001076 (Natural Factors))","forms":["enhanced"],"dose":"130 mg silymarin","doseBasis":"active compound","fed":"standardized breakfast","n":"16","analyte":"total silymarin (free + conjugated, after beta-glucuronidase)","matrix":"capillary whole blood","parameter":"Cmax","detail":"arithmetic mean","value":"284.1","variance":"± 319.3 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"40733088","species":"human","arm":"","form":"Soft-gelatin capsule, liquid; anhydrous self-emulsifying system with MCT and phosphatidylcholine (LipoMicel Milk Thistle, Lot 2001076 (Natural Factors))","forms":["enhanced"],"dose":"130 mg silymarin","doseBasis":"active compound","fed":"standardized breakfast","n":"16","analyte":"total silymarin (free + conjugated, after beta-glucuronidase)","matrix":"capillary whole blood","parameter":"Cmax","detail":"","value":"146.4","variance":"","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Abstract also prints CI 74.4–288.3 ng/mL"},{"pmid":"40733088","species":"human","arm":"","form":"Hard-gelatin capsule, powder (Organika Health Products Milk Thistle, Lot 100284)","forms":["silymarin"],"dose":"130 mg silymarin","doseBasis":"active compound","fed":"standardized breakfast","n":"16","analyte":"total silymarin (free + conjugated, after beta-glucuronidase)","matrix":"capillary whole blood","parameter":"AUC","detail":"AUC0-24h, arithmetic mean","value":"183.6","variance":"± 244.9 (SD)","units":"ng·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"40733088","species":"human","arm":"","form":"Hard-gelatin capsule, powder (Organika Health Products Milk Thistle, Lot 100284)","forms":["silymarin"],"dose":"130 mg silymarin","doseBasis":"active compound","fed":"standardized breakfast","n":"16","analyte":"total silymarin (free + conjugated, after beta-glucuronidase)","matrix":"capillary whole blood","parameter":"AUC","detail":"AUC0-24h","value":"28.9","variance":"","units":"ng·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Abstract prints lower bound as 7.40 and upper 113.5"},{"pmid":"40733088","species":"human","arm":"","form":"Soft-gelatin capsule, liquid; anhydrous self-emulsifying system with MCT and phosphatidylcholine (LipoMicel Milk Thistle, Lot 2001076 (Natural Factors))","forms":["enhanced"],"dose":"130 mg silymarin","doseBasis":"active compound","fed":"standardized breakfast","n":"16","analyte":"total silymarin (free + conjugated, after beta-glucuronidase)","matrix":"capillary whole blood","parameter":"AUC","detail":"AUC0-24h, arithmetic mean","value":"544.6","variance":"± 485.5 (SD)","units":"ng·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"40733088","species":"human","arm":"","form":"Soft-gelatin capsule, liquid; anhydrous self-emulsifying system with MCT and phosphatidylcholine (LipoMicel Milk Thistle, Lot 2001076 (Natural Factors))","forms":["enhanced"],"dose":"130 mg silymarin","doseBasis":"active compound","fed":"standardized breakfast","n":"16","analyte":"total silymarin (free + conjugated, after beta-glucuronidase)","matrix":"capillary whole blood","parameter":"AUC","detail":"AUC0-24h","value":"330.4","variance":"","units":"ng·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Abstract prints CI as 178–612.5"},{"pmid":"11529693","species":"rodent","arm":"","form":"125I-silibinin derivative 1 (125I-SB1) + unlabeled silibinin (Galena Pharmaceuticals (Opava, Czech Republic) supplied labeled compounds)","forms":[],"dose":"5.0 mg unlabeled silibinin/kg body weight (given with 125I-labeled tracer in 2.5 ml solution/kg)","doseBasis":"active compound","fed":"overnight fasted","n":"3-5","analyte":"125I radioactivity derived from 125I-SB1","matrix":"blood","parameter":"AUC","detail":"AUC0-210 min","value":"257.60","variance":"± 42.69 (SEM)","units":"min %","location":"Results p.2","quote":"AUC 257.60 ± 42.69 vs 1382.30 ± 60.20, P< 0.01, and RAmax 2.24 ± 0.68 vs 8.62 ± 0.92, P< 0.01","quoteCheck":"supported","note":"Units 'min %' from Fig. 2 caption (AUC210 = area under the curve up to 210 minute (min %)); text value printed without units; SE per figure legend (±)"},{"pmid":"11529693","species":"rodent","arm":"","form":"125I-SB1 + unlabeled silibinin (Galena Pharmaceuticals (Opava, Czech Republic) supplied labeled compounds)","forms":[],"dose":"50 mg unlabeled silibinin/kg body weight (given with 125I-labeled tracer in 2.5 ml solution/kg)","doseBasis":"active compound","fed":"overnight fasted","n":"3-5","analyte":"125I radioactivity derived from 125I-SB1","matrix":"blood","parameter":"AUC","detail":"AUC0-210 min","value":"1382.30","variance":"± 60.20 (SEM)","units":"min %","location":"Results p.2","quote":"AUC 257.60 ± 42.69 vs 1382.30 ± 60.20, P< 0.01, and RAmax 2.24 ± 0.68 vs 8.62 ± 0.92, P< 0.01","quoteCheck":"supported","note":"Units from Fig. 2 caption; SE per figure legend (±)"},{"pmid":"11529693","species":"rodent","arm":"","form":"125I-silibinin derivative 1 (125I-SB1) + unlabeled silibinin (Galena Pharmaceuticals (Opava, Czech Republic) supplied labeled compounds)","forms":[],"dose":"5.0 mg unlabeled silibinin/kg body weight (given with 125I-labeled tracer in 2.5 ml solution/kg)","doseBasis":"active compound","fed":"overnight fasted","n":"3-5","analyte":"125I radioactivity derived from 125I-SB1","matrix":"blood","parameter":"Cmax","detail":"RAmax: maximal percentage of administered radioactivity in blood","value":"2.24","variance":"± 0.68 (SEM)","units":"% of administered radioactivity","location":"Results p.2","quote":"AUC 257.60 ± 42.69 vs 1382.30 ± 60.20, P< 0.01, and RAmax 2.24 ± 0.68 vs 8.62 ± 0.92, P< 0.01","quoteCheck":"supported","note":"Units from Fig. 2 caption (RAmax = maximum percentage of administered radioactivity found in the blood (%)); SE per figure legend"},{"pmid":"11529693","species":"rodent","arm":"","form":"125I-SB1 + unlabeled silibinin (Galena Pharmaceuticals (Opava, Czech Republic) supplied labeled compounds)","forms":[],"dose":"50 mg unlabeled silibinin/kg body weight (given with 125I-labeled tracer in 2.5 ml solution/kg)","doseBasis":"active compound","fed":"overnight fasted","n":"3-5","analyte":"125I radioactivity derived from 125I-SB1","matrix":"blood","parameter":"Cmax","detail":"RAmax: maximal percentage of administered radioactivity in blood","value":"8.62","variance":"± 0.92 (SEM)","units":"% of administered radioactivity","location":"Results p.2","quote":"AUC 257.60 ± 42.69 vs 1382.30 ± 60.20, P< 0.01, and RAmax 2.24 ± 0.68 vs 8.62 ± 0.92, P< 0.01","quoteCheck":"supported","note":"Units from Fig. 2 caption; SE per figure legend"},{"pmid":"12748991","species":"rodent","arm":"","form":"NR","forms":[],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"NR","analyte":"125I-silibinin derived radioactivity (RA)","matrix":"plasma","parameter":"Tmax","detail":"time of maximal radioactivity in blood and plasma (range)","value":"30-60","variance":"","units":"min","location":"Results p.3","quote":"reaching maximal levels within 30-60 min","quoteCheck":"supported","note":"Olive-oil vs saline groups; value printed as 'within 30-60 min'"},{"pmid":"12748991","species":"rodent","arm":"","form":"NR","forms":[],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"NR","analyte":"125I-silibinin derived radioactivity (RA)","matrix":"liver and subcellular fractions","parameter":"Tmax","detail":"time of maximal radioactivity in liver (range)","value":"30-60","variance":"","units":"min","location":"Discussion p.4","quote":"the radioactivities reached their maximum levels within 30-60 min","quoteCheck":"supported","note":""},{"pmid":"12748991","species":"rodent","arm":"","form":"NR","forms":[],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"NR","analyte":"125I-silibinin derived radioactivity (RA)","matrix":"extrahepatic tissues","parameter":"Tmax","detail":"time of peak radioactivity in extrahepatic tissues (range)","value":"30-60","variance":"","units":"min","location":"Discussion p.6","quote":"peak levels within 30-60 min indicating rapid tissue distribution","quoteCheck":"supported","note":""},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-phospholipid complex (1:1 w/w silybin:phospholipid; silybin content 49.73% w/w), suspended in 2 ml water","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.17","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Text: Tmax 'derived directly from the experimental points'; text gives about 10 min (PC) and about 5 min (NMG)."},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-phospholipid complex (1:1 w/w silybin:phospholipid; silybin content 49.73% w/w), suspended in 2 ml water","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"126.72","variance":"","units":"ng ml-1","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Text: 'average values of Cmax'"},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-phospholipid complex (1:1 w/w silybin:phospholipid; silybin content 49.73% w/w), suspended in 2 ml water","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC (model-based; interval not stated)","value":"1220.33","variance":"","units":"ng ml-1 h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Abstract prints AUC0-inf 1020.33 for PC; Table 3 prints 1220.33 (inconsistent). Table 3 AUC interval not stated."},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-N-methylglucamine suspension/solution","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.08","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Text: Tmax 'derived directly from the experimental points'; text gives about 10 min (PC) and about 5 min (NMG)."},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-N-methylglucamine suspension/solution","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"104.29","variance":"","units":"ng ml-1","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Text: 'average values of Cmax'"},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-N-methylglucamine suspension/solution","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC (model-based; interval not stated)","value":"235.81","variance":"","units":"ng ml-1 h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 AUC interval not stated."},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-phospholipid complex (1:1 w/w silybin:phospholipid; silybin content 49.73% w/w), suspended in 2 ml water","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf (abstract)","value":"1020.33","variance":"","units":"ng ml-1 h","location":"Abstract","quote":"AUC0–∞ 1020.33 and 235.81 ng ml−1 h, respectively","quoteCheck":"supported","note":"Inconsistent with Table 3 (1220.33) and Table 4 AUC(0-inf) 1429.56."},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-N-methylglucamine suspension/solution","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf (abstract)","value":"235.81","variance":"","units":"ng ml-1 h","location":"Abstract","quote":"AUC0–∞ 1020.33 and 235.81 ng ml−1 h, respectively","quoteCheck":"supported","note":"Table 4 prints AUC(0-inf) 363.24 for NMG (non-model)."},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-phospholipid complex (1:1 w/w silybin:phospholipid; silybin content 49.73% w/w), suspended in 2 ml water","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"Tmax (abstract/text)","value":"10","variance":"","units":"min","location":"Abstract / Results 3.7","quote":"Tmax 10 and 5 min","quoteCheck":"supported","note":"Text says 'about 10 min'."},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-N-methylglucamine suspension/solution","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"Tmax (abstract/text)","value":"5","variance":"","units":"min","location":"Abstract / Results 3.7","quote":"Tmax 10 and 5 min","quoteCheck":"supported","note":"Text says 'about 5 min'."},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-phospholipid complex (1:1 w/w silybin:phospholipid; silybin content 49.73% w/w), suspended in 2 ml water","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"Cmax (text)","value":"126.72","variance":"","units":"ng ml-1","location":"Results 3.7","quote":"average values of Cmax is 126.72 ng ml−1","quoteCheck":"supported","note":""},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-N-methylglucamine suspension/solution","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"Cmax (text)","value":"104.29","variance":"","units":"ng ml-1","location":"Results 3.7","quote":"average value of Cmax was 104.29 ng ml−1","quoteCheck":"supported","note":""},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-phospholipid complex (1:1 w/w silybin:phospholipid; silybin content 49.73% w/w), suspended in 2 ml water","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(s0) T(0-8 h), non-compartmental (non-model)","value":"1059.02","variance":"","units":"ng ml-1 h","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-phospholipid complex (1:1 w/w silybin:phospholipid; silybin content 49.73% w/w), suspended in 2 ml water","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(s0) T(0-inf), non-compartmental (non-model)","value":"1429.56","variance":"","units":"ng ml-1 h","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-N-methylglucamine suspension/solution","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(s0) T(0-8 h), non-compartmental (non-model)","value":"233.19","variance":"","units":"ng ml-1 h","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16300915","species":"rodent","arm":"","form":"Silybin-N-methylglucamine suspension/solution","forms":[],"dose":"9.1 mg/kg silybin equivalent","doseBasis":"elemental","fed":"fasted 12 h (in vivo)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(s0) T(0-inf), non-compartmental (non-model)","value":"363.24","variance":"","units":"ng ml-1 h","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17328246","species":"rodent","arm":"","form":"Legalon capsule (silymarin) (Legalon (Bukwang))","forms":["silymarin"],"dose":"140 mg/kg as silymarin","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.10","variance":"± 0.48 (SEM)","units":"h","location":"Table II","quote":"Tmax, h 1.10 ± 0.48 (reference capsule)","quoteCheck":"supported","note":""},{"pmid":"17328246","species":"rodent","arm":"","form":"SMEDDS","forms":["enhanced"],"dose":"140 mg/kg as silymarin","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.50","variance":"± 0.00 (SEM)","units":"h","location":"Table II","quote":"Tmax, h 0.50 ± 0.00 (SMEDDS)","quoteCheck":"supported","note":"Dagger: significantly different from reference capsule"},{"pmid":"17328246","species":"rodent","arm":"","form":"Legalon capsule (silymarin) (Legalon (Bukwang))","forms":["silymarin"],"dose":"140 mg/kg as silymarin","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"3.47","variance":"± 0.20 (SEM)","units":"µg/mL","location":"Table II","quote":"Cmax, µg/mL 3.47 ± 0.20","quoteCheck":"supported","note":""},{"pmid":"17328246","species":"rodent","arm":"","form":"SMEDDS","forms":["enhanced"],"dose":"140 mg/kg as silymarin","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"24.79","variance":"± 4.69 (SEM)","units":"µg/mL","location":"Table II","quote":"Cmax, µg/mL 24.79 ± 4.69","quoteCheck":"supported","note":"Dagger: significantly different from reference capsule"},{"pmid":"17328246","species":"rodent","arm":"","form":"Legalon capsule (silymarin) (Legalon (Bukwang))","forms":["silymarin"],"dose":"140 mg/kg as silymarin","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h (trapezoidal)","value":"22.75","variance":"± 3.19 (SEM)","units":"µg·h/mL","location":"Table II","quote":"AUC, µg·h/mL 22.75 ± 3.19","quoteCheck":"supported","note":"AUC interval stated in Methods as zero to 24 h"},{"pmid":"17328246","species":"rodent","arm":"","form":"SMEDDS","forms":["enhanced"],"dose":"140 mg/kg as silymarin","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h (trapezoidal)","value":"81.88","variance":"± 12.86 (SEM)","units":"µg·h/mL","location":"Table II","quote":"AUC, µg·h/mL 81.88 ± 12.86","quoteCheck":"supported","note":"Dagger: significantly different from reference capsule"},{"pmid":"17328246","species":"rodent","arm":"","form":"SMEDDS","forms":["enhanced"],"dose":"140 mg/kg as silymarin","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative BA of SMEDDS vs reference capsule (AUC-based, dose-adjusted)","value":"360","variance":"","units":"%","location":"Results p.87 (Pharmacokinetic study)","quote":"The calculated relative bioavailability of the SMEDDS compared to the reference capsule was 360%.","quoteCheck":"supported","note":"Abstract: 'bioavailability ... 3.6 times higher'"},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin dissolved in ethanol:PEG 200 (1:1) (Sigma)","forms":[],"dose":"100 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Unconjugated silibinin","matrix":"plasma (blood)","parameter":"AUC","detail":"AUC (observed sampling interval not stated)","value":"5.5","variance":"± 0.73 (SEM)","units":"min mg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin dissolved in ethanol:PEG 200 (1:1) (Sigma)","forms":[],"dose":"100 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Unconjugated silibinin","matrix":"plasma (blood)","parameter":"Cmax","detail":"","value":"256","variance":"± 36 (SEM)","units":"µg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin dissolved in ethanol:PEG 200 (1:1) (Sigma)","forms":[],"dose":"100 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Unconjugated silibinin","matrix":"plasma (blood)","parameter":"Tmax","detail":"","value":"0","variance":"± 0 (no variance printed) (SEM)","units":"not printed in Table 4","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Tmax unit not printed in Table 4; text gives min for bile Tmax"},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin dissolved in ethanol:PEG 200 (1:1) (Sigma)","forms":[],"dose":"100 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Total silibinin (after beta-glucuronidase)","matrix":"plasma (blood)","parameter":"AUC","detail":"AUC (observed sampling interval not stated)","value":"35.5","variance":"± 5.9 (SEM)","units":"min mg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin dissolved in ethanol:PEG 200 (1:1) (Sigma)","forms":[],"dose":"100 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Total silibinin (after beta-glucuronidase)","matrix":"plasma (blood)","parameter":"Cmax","detail":"","value":"239","variance":"± 19 (SEM)","units":"µg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin dissolved in ethanol:PEG 200 (1:1) (Sigma)","forms":[],"dose":"100 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Total silibinin (after beta-glucuronidase)","matrix":"plasma (blood)","parameter":"Tmax","detail":"","value":"8.2","variance":"± 4.5 (SEM)","units":"not printed in Table 4","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Tmax unit not printed in Table 4; text gives min for bile Tmax"},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin (Sigma)","forms":[],"dose":"500 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Unconjugated silibinin","matrix":"plasma (blood)","parameter":"AUC","detail":"AUC (observed sampling interval not stated)","value":"0.26","variance":"± 0.07 (SEM)","units":"min mg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin (Sigma)","forms":[],"dose":"500 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Unconjugated silibinin","matrix":"plasma (blood)","parameter":"Cmax","detail":"","value":"8.5","variance":"± 2.6 (SEM)","units":"µg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin (Sigma)","forms":[],"dose":"500 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Unconjugated silibinin","matrix":"plasma (blood)","parameter":"Tmax","detail":"","value":"11","variance":"± 1.8 (SEM)","units":"not printed in Table 4","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Tmax unit not printed in Table 4; text gives min for bile Tmax"},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin (Sigma)","forms":[],"dose":"500 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Total silibinin (after beta-glucuronidase)","matrix":"plasma (blood)","parameter":"AUC","detail":"AUC (observed sampling interval not stated)","value":"7.17","variance":"± 1.42 (SEM)","units":"min mg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin (Sigma)","forms":[],"dose":"500 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Total silibinin (after beta-glucuronidase)","matrix":"plasma (blood)","parameter":"Cmax","detail":"","value":"76","variance":"± 15 (SEM)","units":"µg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin (Sigma)","forms":[],"dose":"500 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Total silibinin (after beta-glucuronidase)","matrix":"plasma (blood)","parameter":"Tmax","detail":"","value":"30","variance":"± 4.7 (SEM)","units":"not printed in Table 4","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Tmax unit not printed in Table 4; text gives min for bile Tmax"},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin dissolved in ethanol:PEG 200 (1:1) (Sigma)","forms":[],"dose":"100 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Unconjugated silibinin","matrix":"bile","parameter":"AUC","detail":"","value":"11.1","variance":"± 2.84 (SEM)","units":"min mg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"17692492","species":"rodent","arm":"","form":"Silibinin dissolved in ethanol:PEG 200 (1:1) (Sigma)","forms":[],"dose":"100 mg/kg","doseBasis":"active compound","fed":"food removed 18 h prior","n":"6","analyte":"Total silibinin (after beta-glucuronidase)","matrix":"bile","parameter":"AUC","detail":"","value":"1202","variance":"± 186 (SEM)","units":"min mg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"10 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval NR)","value":"0.16","variance":"± 0.03 (SEM)","units":"min·mg/ml","location":"Table 1","quote":"AUC 0.16 ± 0.03","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"10 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"28","variance":"± 8 (SEM)","units":"µg/ml","location":"Table 1","quote":"Cmax 28 ± 8","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"10 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"bile","parameter":"Tmax","detail":"","value":"1","variance":"± 0 (SEM)","units":"min","location":"Table 1","quote":"Tmax 1 ± 0","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"10 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval NR)","value":"3.11","variance":"± 0.81 (SEM)","units":"min·mg/ml","location":"Table 1","quote":"AUC 3.11 ± 0.81","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"10 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"37","variance":"± 15 (SEM)","units":"µg/ml","location":"Table 1","quote":"Cmax 37 ± 15","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"10 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"bile","parameter":"Tmax","detail":"","value":"6.3","variance":"± 1.1 (SEM)","units":"min","location":"Table 1","quote":"Tmax 6.3 ± 1.1","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval NR)","value":"1.5","variance":"± 0.24 (SEM)","units":"min·mg/ml","location":"Table 2","quote":"AUC 1.5 ± 0.24","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"92","variance":"± 7 (SEM)","units":"µg/ml","location":"Table 2","quote":"Cmax 92 ± 7","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"bile","parameter":"Tmax","detail":"","value":"3","variance":"± 0.98 (SEM)","units":"min","location":"Table 2","quote":"Tmax 3 ± 0.98","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval NR)","value":"19.8","variance":"± 4.9 (SEM)","units":"min·mg/ml","location":"Table 2","quote":"AUC 19.8 ± 4.9","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"89","variance":"± 8.3 (SEM)","units":"µg/ml","location":"Table 2","quote":"Cmax 89 ± 8.3","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"bile","parameter":"Tmax","detail":"","value":"14","variance":"± 4.6 (SEM)","units":"min","location":"Table 2","quote":"Tmax 14 ± 4.6","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval NR)","value":"0.2","variance":"± 0.04 (SEM)","units":"min·mg/ml","location":"Table 2","quote":"AUC 0.2 ± 0.04*","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"38","variance":"± 11 (SEM)","units":"µg/ml","location":"Table 2","quote":"Cmax 38 ± 11*","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"bile","parameter":"Tmax","detail":"","value":"4.7","variance":"± 1.8 (SEM)","units":"min","location":"Table 2","quote":"Tmax 4.7 ± 1.8","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval NR)","value":"35","variance":"± 2.8 (SEM)","units":"min·mg/ml","location":"Table 2","quote":"AUC 35 ± 2.8*","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"113","variance":"± 29 (SEM)","units":"µg/ml","location":"Table 2","quote":"Cmax 113 ± 29","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"30 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"bile","parameter":"Tmax","detail":"","value":"10.7","variance":"± 2.2 (SEM)","units":"min","location":"Table 2","quote":"Tmax 10.7 ± 2.2","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval NR)","value":"1.3","variance":"± 0.2 (SEM)","units":"min·mg/ml","location":"Table 3","quote":"AUC 1.3 ± 0.2","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"143","variance":"± 35 (SEM)","units":"µg/ml","location":"Table 3","quote":"Cmax 143 ± 35","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"bile","parameter":"Tmax","detail":"","value":"2.3","variance":"± 1.1 (SEM)","units":"min","location":"Table 3","quote":"Tmax 2.3 ± 1.1","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval NR)","value":"29","variance":"± 1.2 (SEM)","units":"min·mg/ml","location":"Table 3","quote":"AUC 29 ± 1.2","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"133","variance":"± 9.8 (SEM)","units":"µg/ml","location":"Table 3","quote":"Cmax 133 ± 9.8","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"bile","parameter":"Tmax","detail":"","value":"22.5","variance":"± 4.7 (SEM)","units":"min","location":"Table 3","quote":"Tmax 22.5 ± 4.7","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval NR)","value":"0.7","variance":"± 0.04 (SEM)","units":"min·mg/ml","location":"Table 3","quote":"AUC 0.7 ± 0.04*","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"83","variance":"± 12 (SEM)","units":"µg/ml","location":"Table 3","quote":"Cmax 83 ± 12","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"unconjugated silibinin","matrix":"bile","parameter":"Tmax","detail":"","value":"3.7","variance":"± 1.1 (SEM)","units":"min","location":"Table 3","quote":"Tmax 3.7 ± 1.1","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval NR)","value":"53","variance":"± 11 (SEM)","units":"min·mg/ml","location":"Table 3","quote":"AUC 53 ± 11*","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"145","variance":"± 6.2 (SEM)","units":"µg/ml","location":"Table 3","quote":"Cmax 145 ± 6.2","quoteCheck":"supported","note":""},{"pmid":"18048488","species":"rodent","arm":"","form":"Silibinin i.v. in ethanol:PEG 200 (1:1) (Sigma-Aldrich)","forms":[],"dose":"50 mg/kg i.v.","doseBasis":"active compound","fed":"food removed 18 h before","n":"6","analyte":"total silibinin","matrix":"bile","parameter":"Tmax","detail":"","value":"35","variance":"± 3.9 (SEM)","units":"min","location":"Table 3","quote":"Tmax 35 ± 3.9*","quoteCheck":"supported","note":""},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Tmax","detail":"","value":"1.00","variance":"","units":"h","location":"Table 3","quote":"tmax (h) 1.00","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"","value":"0.93","variance":"","units":"µg/mL","location":"Table 3","quote":"Cmax (µg/mL) 0.93","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast","value":"0.63","variance":"","units":"h × µg/mL","location":"Table 3","quote":"AUClast (h × µg/mL) 0.63","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"dose-normalized","value":"0.11","variance":"","units":"µg/mL","location":"Table 3","quote":"Dose-normalized Cmax 0.11","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast, dose-normalized","value":"0.07","variance":"","units":"h × µg/mL","location":"Table 3","quote":"Dose-normalized AUClast 0.07","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"relative_bioavailability","detail":"Frel (PVP-CL or Ac-Di-Sol coground vs extract), dose-normalized AUC ratio","value":"1","variance":"","units":"ratio (fold, as printed; reference extract = 1)","location":"Table 3","quote":"Frel 1","quoteCheck":"supported","note":"Reference arm printed as 1"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Tmax","detail":"","value":"0.50","variance":"","units":"h","location":"Table 3","quote":"tmax (h) 0.50","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"","value":"3.00","variance":"","units":"µg/mL","location":"Table 3","quote":"Cmax (µg/mL) 3.00","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast","value":"6.70","variance":"","units":"h × µg/mL","location":"Table 3","quote":"AUClast (h × µg/mL) 6.70","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"dose-normalized","value":"1.15","variance":"","units":"µg/mL","location":"Table 3","quote":"Dose-normalized Cmax 1.15","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast, dose-normalized","value":"2.58","variance":"","units":"h × µg/mL","location":"Table 3","quote":"Dose-normalized AUClast 2.58","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"relative_bioavailability","detail":"Frel (PVP-CL or Ac-Di-Sol coground vs extract), dose-normalized AUC ratio","value":"34.5","variance":"","units":"ratio (fold, as printed; reference extract = 1)","location":"Table 3","quote":"Frel 34.5","quoteCheck":"supported","note":"Abstract/Results state same value"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Tmax","detail":"","value":"1.00","variance":"","units":"h","location":"Table 3","quote":"tmax (h) 1.00","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"","value":"7.66","variance":"","units":"µg/mL","location":"Table 3","quote":"Cmax (µg/mL) 7.66","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast","value":"17.20","variance":"","units":"h × µg/mL","location":"Table 3","quote":"AUClast (h × µg/mL) 17.20","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"dose-normalized","value":"2.95","variance":"","units":"µg/mL","location":"Table 3","quote":"Dose-normalized Cmax 2.95","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast, dose-normalized","value":"6.61","variance":"","units":"h × µg/mL","location":"Table 3","quote":"Dose-normalized AUClast 6.61","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin A","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"relative_bioavailability","detail":"Frel (PVP-CL or Ac-Di-Sol coground vs extract), dose-normalized AUC ratio","value":"88.6","variance":"","units":"ratio (fold, as printed; reference extract = 1)","location":"Table 3","quote":"Frel 88.6","quoteCheck":"supported","note":"Abstract/Results state same value"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Tmax","detail":"","value":"1.00","variance":"","units":"h","location":"Table 3","quote":"tmax (h) 1.00","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"","value":"1.67","variance":"","units":"µg/mL","location":"Table 3","quote":"Cmax (µg/mL) 1.67","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast","value":"3.79","variance":"","units":"h × µg/mL","location":"Table 3","quote":"AUClast (h × µg/mL) 3.79","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"dose-normalized","value":"0.21","variance":"","units":"µg/mL","location":"Table 3","quote":"Dose-normalized Cmax 0.21","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast, dose-normalized","value":"0.47","variance":"","units":"h × µg/mL","location":"Table 3","quote":"Dose-normalized AUClast 0.47","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"relative_bioavailability","detail":"Frel (PVP-CL or Ac-Di-Sol coground vs extract), dose-normalized AUC ratio","value":"1","variance":"","units":"ratio (fold, as printed; reference extract = 1)","location":"Table 3","quote":"Frel 1","quoteCheck":"supported","note":"Reference arm printed as 1"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Tmax","detail":"","value":"1.00","variance":"","units":"h","location":"Table 3","quote":"tmax (h) 1.00","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"","value":"4.43","variance":"","units":"µg/mL","location":"Table 3","quote":"Cmax (µg/mL) 4.43","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast","value":"12.90","variance":"","units":"h × µg/mL","location":"Table 3","quote":"AUClast (h × µg/mL) 12.90","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"dose-normalized","value":"1.97","variance":"","units":"µg/mL","location":"Table 3","quote":"Dose-normalized Cmax 1.97","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast, dose-normalized","value":"5.73","variance":"","units":"h × µg/mL","location":"Table 3","quote":"Dose-normalized AUClast 5.73","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (PVP-CL (BASF/Euphar))","forms":[],"dose":"50 mg/kg coground system (= 2.6 and 2.25 mg/kg silybin A, silybin B)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"relative_bioavailability","detail":"Frel (PVP-CL or Ac-Di-Sol coground vs extract), dose-normalized AUC ratio","value":"12.1","variance":"","units":"ratio (fold, as printed; reference extract = 1)","location":"Table 3","quote":"Frel 12.1","quoteCheck":"supported","note":"Abstract/Results state same value"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Tmax","detail":"","value":"1.00","variance":"","units":"h","location":"Table 3","quote":"tmax (h) 1.00","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"","value":"7.69","variance":"","units":"µg/mL","location":"Table 3","quote":"Cmax (µg/mL) 7.69","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast","value":"19.15","variance":"","units":"h × µg/mL","location":"Table 3","quote":"AUClast (h × µg/mL) 19.15","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"dose-normalized","value":"3.42","variance":"","units":"µg/mL","location":"Table 3","quote":"Dose-normalized Cmax 3.42","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast, dose-normalized","value":"8.51","variance":"","units":"h × µg/mL","location":"Table 3","quote":"Dose-normalized AUClast 8.51","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silybin B","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"relative_bioavailability","detail":"Frel (PVP-CL or Ac-Di-Sol coground vs extract), dose-normalized AUC ratio","value":"17.96","variance":"","units":"ratio (fold, as printed; reference extract = 1)","location":"Table 3","quote":"Frel 17.96","quoteCheck":"supported","note":"Abstract/Results state same value"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Tmax","detail":"","value":"1.00","variance":"","units":"h","location":"Table 3","quote":"tmax (h) 1.00","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"","value":"0.63","variance":"","units":"µg/mL","location":"Table 3","quote":"Cmax (µg/mL) 0.63","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast","value":"0.72","variance":"","units":"h × µg/mL","location":"Table 3","quote":"AUClast (h × µg/mL) 0.72","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"dose-normalized","value":"0.06","variance":"","units":"µg/mL","location":"Table 3","quote":"Dose-normalized Cmax 0.06","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast, dose-normalized","value":"0.07","variance":"","units":"h × µg/mL","location":"Table 3","quote":"Dose-normalized AUClast 0.07","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"dry extract, aqueous suspension, gastric gavage (Indena S.p.A.)","forms":[],"dose":"50 mg/kg extract (= 8.5, 8, 10.5 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"relative_bioavailability","detail":"Frel (PVP-CL or Ac-Di-Sol coground vs extract), dose-normalized AUC ratio","value":"1","variance":"","units":"ratio (fold, as printed; reference extract = 1)","location":"Table 3","quote":"Frel 1","quoteCheck":"supported","note":"Reference arm printed as 1"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Tmax","detail":"","value":"1.00","variance":"","units":"h","location":"Table 3","quote":"tmax (h) 1.00","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"","value":"1.85","variance":"","units":"µg/mL","location":"Table 3","quote":"Cmax (µg/mL) 1.85","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast","value":"5.02","variance":"","units":"h × µg/mL","location":"Table 3","quote":"AUClast (h × µg/mL) 5.02","quoteCheck":"supported","note":"Pharmacokinetic parameters calculated on composite plasma curves (Methods); no variance reported"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"Cmax","detail":"dose-normalized","value":"0.42","variance":"","units":"µg/mL","location":"Table 3","quote":"Dose-normalized Cmax 0.42","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"AUC","detail":"AUClast, dose-normalized","value":"1.13","variance":"","units":"h × µg/mL","location":"Table 3","quote":"Dose-normalized AUClast 1.13","quoteCheck":"supported","note":"Dose-normalized value as printed by authors (not calculated by extractor)"},{"pmid":"18428992","species":"rodent","arm":"","form":"coground system, aqueous suspension, gavage (Ac-Di-Sol (Shilling))","forms":[],"dose":"50 mg/kg coground system (= 2.6, 2.25, 4.45 mg/kg silybin A, silybin B, silychristin)","doseBasis":"salt/compound","fed":"fasted overnight","n":"NR","analyte":"silychristin","matrix":"plasma (serum per Methods; total after glucuronidase/arylsulfatase)","parameter":"relative_bioavailability","detail":"Frel (PVP-CL or Ac-Di-Sol coground vs extract), dose-normalized AUC ratio","value":"16.4","variance":"","units":"ratio (fold, as printed; reference extract = 1)","location":"Table 3","quote":"Frel 16.4","quoteCheck":"supported","note":"Abstract/Results state same value"},{"pmid":"19226635","species":"rodent","arm":"","form":"Commercial S. marianum capsule (at least 200 mg flavonoids as silymarin), given as powder in aqueous suspension (Silirex 200 (Lampugnani Farmaceutici))","forms":["silymarin"],"dose":"200 mg/kg silymarin","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin (total, plasma)","matrix":"plasma","parameter":"Cmax","detail":"","value":"4.1","variance":"","units":"mg/L","location":"Table 2","quote":"maximal concentration of 33.2 mg/L compared to 4.1 mg/L obtained with Silirex","quoteCheck":"supported","note":"PK parameters calculated on composite plasma curves"},{"pmid":"19226635","species":"rodent","arm":"","form":"Commercial S. marianum capsule (at least 200 mg flavonoids as silymarin), given as powder in aqueous suspension (Silirex 200 (Lampugnani Farmaceutici))","forms":["silymarin"],"dose":"200 mg/kg silymarin","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin (total, plasma)","matrix":"plasma","parameter":"Tmax","detail":"observed","value":"1.72","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Methods: tmax reported as observed; sampling only at 1, 2, 4 h yet value printed is 1.72"},{"pmid":"19226635","species":"rodent","arm":"","form":"Commercial S. marianum capsule (at least 200 mg flavonoids as silymarin), given as powder in aqueous suspension (Silirex 200 (Lampugnani Farmaceutici))","forms":["silymarin"],"dose":"200 mg/kg silymarin","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin (total, plasma)","matrix":"plasma","parameter":"AUC","detail":"AUClast (log-linear trapezoidal)","value":"16.2","variance":"","units":"mgh/L","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Unit printed as mgh/L in Table 2 (page image checked)"},{"pmid":"19226635","species":"rodent","arm":"","form":"Commercial S. marianum capsule (at least 200 mg flavonoids as silymarin), given as powder in aqueous suspension (Silirex 200 (Lampugnani Farmaceutici))","forms":["silymarin"],"dose":"200 mg/kg silymarin","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin (total, plasma)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel = AUC(formulation)/AUC(commercial); reference","value":"1","variance":"","units":"","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19226635","species":"rodent","arm":"","form":"S. marianum dry extract (Indena) co-ground with betacyclodextrins in planetary mill (1 h), aqueous suspension (Experimental)","forms":[],"dose":"200 mg/kg silymarin","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin (total, plasma)","matrix":"plasma","parameter":"Cmax","detail":"","value":"33.2","variance":"","units":"mg/L","location":"Table 2","quote":"reaching a maximal concentration of 33.2 mg/L compared to 4.1 mg/L obtained with Silirex","quoteCheck":"supported","note":"PK parameters calculated on composite plasma curves"},{"pmid":"19226635","species":"rodent","arm":"","form":"S. marianum dry extract (Indena) co-ground with betacyclodextrins in planetary mill (1 h), aqueous suspension (Experimental)","forms":[],"dose":"200 mg/kg silymarin","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin (total, plasma)","matrix":"plasma","parameter":"Tmax","detail":"observed","value":"2.34","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Methods: tmax reported as observed; sampling only at 1, 2, 4 h yet value printed is 2.34"},{"pmid":"19226635","species":"rodent","arm":"","form":"S. marianum dry extract (Indena) co-ground with betacyclodextrins in planetary mill (1 h), aqueous suspension (Experimental)","forms":[],"dose":"200 mg/kg silymarin","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin (total, plasma)","matrix":"plasma","parameter":"AUC","detail":"AUClast (log-linear trapezoidal)","value":"107.8","variance":"","units":"mgh/L","location":"Table 2; Results p.9","quote":"the AUC is in fact 145.4 mgh/L for sodium croscarmellose, 107.8 mgh/L for BCD","quoteCheck":"supported","note":"Unit printed as mgh/L in Table 2 (page image checked)"},{"pmid":"19226635","species":"rodent","arm":"","form":"S. marianum dry extract (Indena) co-ground with betacyclodextrins in planetary mill (1 h), aqueous suspension (Experimental)","forms":[],"dose":"200 mg/kg silymarin","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin (total, plasma)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel = AUC(formulation)/AUC(commercial)","value":"6.6","variance":"","units":"","location":"Table 2; Abstract; Results p.9","quote":"The oral bioavailability of the coground system was 6.6 times higher than that of the commercial product","quoteCheck":"supported","note":"Pilot study; no formal statistical test"},{"pmid":"19226635","species":"rodent","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silybin (total, plasma), previous study ref 17","matrix":"plasma","parameter":"AUC","detail":"coground with sodium croscarmellose (previous study, ref 17; not an arm of this paper)","value":"145.4","variance":"","units":"mgh/L","location":"Results p.9 (left column)","quote":"the AUC is in fact 145.4 mgh/L for sodium croscarmellose","quoteCheck":"supported","note":"Value from authors' earlier study (ref 17) cited for comparison; not measured in this paper"},{"pmid":"19226635","species":"rodent","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silybin (total, plasma), previous study ref 17","matrix":"plasma","parameter":"AUC","detail":"coground with crospovidone (previous study, ref 17; not an arm of this paper)","value":"78.4","variance":"","units":"mgh/L","location":"Results p.9 (left column)","quote":"78.4 mgh/L for crospovidone","quoteCheck":"supported","note":"Value from authors' earlier study (ref 17) cited for comparison; not measured in this paper"},{"pmid":"19470289","species":"rodent","arm":"","form":"Silymarin (36% silibinin) dissolved in DMA:PEG400:water 4:4:2, infused 1 min via jugular vein","forms":["silymarin"],"dose":"50 mg/kg silymarin (18 mg/kg as silibinin)","doseBasis":"salt/compound","fed":"NR","n":"9","analyte":"unconjugated silibinin","matrix":"plasma (arterial)","parameter":"AUC","detail":"AUC0-inf","value":"740","variance":"± 143 (SD)","units":"μg * min/mL","location":"Table 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1630 (SD)","units":"μg * min/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19470289","species":"rodent","arm":"","form":"Silymarin 50 mg/kg IV with oltipraz 10 mg/kg IV together","forms":["silymarin"],"dose":"50 mg/kg silymarin (18 mg/kg as silibinin) + oltipraz 10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"8","analyte":"unconjugated silibinin","matrix":"plasma (arterial)","parameter":"AUC","detail":"AUC0-inf","value":"498","variance":"± 105 (SD)","units":"μg * min/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19470289","species":"rodent","arm":"","form":"Silymarin 50 mg/kg IV with oltipraz 10 mg/kg IV together","forms":["silymarin"],"dose":"50 mg/kg silymarin (18 mg/kg as silibinin) + oltipraz 10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"8","analyte":"conjugated silibinin (total minus unconjugated)","matrix":"plasma (arterial)","parameter":"AUC","detail":"AUC0-inf","value":"11700","variance":"± 3310 (SD)","units":"μg * min/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19470289","species":"rodent","arm":"","form":"Silymarin 50 mg/kg IV with oltipraz 10 mg/kg IV together","forms":["silymarin"],"dose":"50 mg/kg silymarin (18 mg/kg as silibinin) + oltipraz 10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"8","analyte":"total silibinin (unconjugated + conjugated)","matrix":"plasma (arterial)","parameter":"AUC","detail":"AUC0-inf","value":"12300","variance":"± 3210 (SD)","units":"μg * min/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19470289","species":"rodent","arm":"","form":"Silymarin (36% silibinin) in DMA:PEG400:water solution by gastric gavage","forms":["silymarin"],"dose":"100 mg/kg silymarin (36 mg/kg as silibinin)","doseBasis":"salt/compound","fed":"NR","n":"12","analyte":"unconjugated silibinin","matrix":"plasma (arterial)","parameter":"AUC","detail":"AUC0-inf for conjugated and total; AUC0-12h for 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(SD)","units":"μg/mL","location":"Table 6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19470289","species":"rodent","arm":"","form":"Silymarin daily 14 days; oltipraz 30 mg/kg given with silymarin on 15th day","forms":["silymarin"],"dose":"100 mg/kg/day silymarin (36 mg/kg as silibinin) + oltipraz 30 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"10","analyte":"total silibinin (unconjugated + conjugated)","matrix":"plasma (arterial)","parameter":"Cmax","detail":"","value":"32.5","variance":"± 17.6 (SD)","units":"μg/mL","location":"Table 6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19470289","species":"rodent","arm":"","form":"Silymarin daily oral for 14 days; PK on day 15","forms":["silymarin"],"dose":"100 mg/kg/day silymarin (36 mg/kg as silibinin)","doseBasis":"salt/compound","fed":"NR","n":"8","analyte":"unconjugated silibinin","matrix":"plasma (arterial)","parameter":"Tmax","detail":"","value":"22.5","variance":"","units":"min","location":"Table 6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19470289","species":"rodent","arm":"","form":"Silymarin daily oral for 14 days; PK on day 15","forms":["silymarin"],"dose":"100 mg/kg/day silymarin (36 mg/kg as silibinin)","doseBasis":"salt/compound","fed":"NR","n":"8","analyte":"conjugated silibinin (total minus unconjugated)","matrix":"plasma (arterial)","parameter":"Tmax","detail":"","value":"30","variance":"","units":"min","location":"Table 6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19470289","species":"rodent","arm":"","form":"Silymarin daily oral for 14 days; PK on day 15","forms":["silymarin"],"dose":"100 mg/kg/day silymarin (36 mg/kg as silibinin)","doseBasis":"salt/compound","fed":"NR","n":"8","analyte":"total silibinin (unconjugated + conjugated)","matrix":"plasma (arterial)","parameter":"Tmax","detail":"","value":"30","variance":"","units":"min","location":"Table 6","quote":"","quoteCheck":"no 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quote","note":""},{"pmid":"19863195","species":"rodent","arm":"","form":"Pluronic P105 polymeric micelles loaded with silybin, lyophilized and redispersed in normal saline (1 mg/mL silybin) (Experimental)","forms":["enhanced"],"dose":"6 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(S0); AUC0-inf (area under plasma concentration-time curve)","value":"2.85","variance":"± 0.24 (SD)","units":"μg·mL−1·h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"19863195","species":"rodent","arm":"","form":"Lactobionic acid-conjugated Pluronic P105 micelles loaded with silybin (Experimental)","forms":["enhanced"],"dose":"6 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(S0); AUC0-inf (area under plasma concentration-time curve)","value":"2.28","variance":"± 0.14 (SD)","units":"μg·mL−1·h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20942611","species":"rodent","arm":"","form":"silybin-PAMAM G2 complex","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"15","variance":"± 0.8 (NR)","units":"minute","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance printed as ± value; type (SD/SEM) not stated"},{"pmid":"20942611","species":"rodent","arm":"","form":"silybin suspension in water","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"10","variance":"± 0.7 (NR)","units":"minute","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance printed as ± value; type (SD/SEM) not stated"},{"pmid":"20942611","species":"rodent","arm":"","form":"silybin-PAMAM G2 complex","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"182.4","variance":"± 37.3 (NR)","units":"ng/mL","location":"Table 2","quote":"The administration of silybin-G2 PAMAM mixture achieved a Cmax of 182.4 ng/mL at a Tmax of 15 minutes","quoteCheck":"supported","note":"Variance type not stated"},{"pmid":"20942611","species":"rodent","arm":"","form":"silybin suspension in water","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"134.2","variance":"± 17.6 (NR)","units":"ng/mL","location":"Table 2","quote":"silybin suspension was rapidly absorbed through the rat gastrointestinal tract with a Cmax of 134.2 ng/mL at a Tmax of 10 minutes","quoteCheck":"supported","note":"Variance type not stated"},{"pmid":"20942611","species":"rodent","arm":"","form":"silybin-PAMAM G2 complex","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"959.02","variance":"± 136.4 (NR)","units":"(ng h)/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Marked * (P<0.05 vs suspension); variance type not stated; AUC0-t interval not stated beyond last measurable concentration"},{"pmid":"20942611","species":"rodent","arm":"","form":"silybin suspension in water","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"583.19","variance":"± 98.5 (NR)","units":"(ng h)/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated"},{"pmid":"20942611","species":"rodent","arm":"","form":"silybin-PAMAM G2 complex","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"1298.7","variance":"± 206.4 (NR)","units":"(ng h)/mL","location":"Table 2","quote":"Tmax, Cmax, and AUC0-inf ... 15 minutes, 182.4 ng/mL, 1298.7 (ng·h)/mL","quoteCheck":"supported","note":"Marked * (P<0.05 vs suspension); variance type not stated"},{"pmid":"20942611","species":"rodent","arm":"","form":"silybin suspension in water","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"654.6","variance":"± 120.7 (NR)","units":"(ng h)/mL","location":"Table 2","quote":"10 minutes, 134.2 ng/mL, 654.6 (ng·h)/mL","quoteCheck":"supported","note":"Variance type not stated"},{"pmid":"20942611","species":"rodent","arm":"","form":"silybin-PAMAM G2 complex","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"based on AUC0-inf, vs silybin suspension","value":"178.2","variance":"± 26.78 (NR)","units":"%","location":"Table 2","quote":"the oral bioavailability of silybin-G2 PAMAM mixture was about 178% as compared with that of silybin suspension","quoteCheck":"value not in quote","note":"Text and abstract print about 178%; Table 2 prints 178.2 +/- 26.78 (marked *)"},{"pmid":"20942611","species":"rodent","arm":"","form":"silybin suspension in water","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"reference","value":"100","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Reference value"},{"pmid":"21111585","species":"rodent","arm":"","form":"milk thistle dry extract in 0.9% NaCl solution (Indena extract)","forms":["silymarin"],"dose":"25.41 mg silybin A + 28.66 mg silybin B (total silybin 54.07 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin A","matrix":"plasma","parameter":"Tmax","detail":"t_max","value":"30","variance":"± 0 (SD)","units":"min","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"milk thistle dry extract in 0.9% NaCl solution (Indena extract)","forms":["silymarin"],"dose":"25.41 mg silybin A + 28.66 mg silybin B (total silybin 54.07 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.2713","variance":"± 0.0101 (SD)","units":"µg/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"milk thistle dry extract in 0.9% NaCl solution (Indena extract)","forms":["silymarin"],"dose":"25.41 mg silybin A + 28.66 mg silybin B (total silybin 54.07 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin A","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"9.84","variance":"± 0.52 (SD)","units":"µg h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"milk thistle dry extract in 0.9% NaCl solution (Indena extract)","forms":["silymarin"],"dose":"25.41 mg silybin A + 28.66 mg silybin B (total silybin 54.07 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin A","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"10.34","variance":"± 0.74 (SD)","units":"µg min/ml","location":"Table 3","quote":"","quoteCheck":"no 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compound","fed":"fed","n":"4","analyte":"Silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"14.1833","variance":"± 2.0116 (SD)","units":"µg/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"silymarin (Indena milk thistle dry extract, 83% w/w silybin) in solid self-emulsifying pellets (Indena extract)","forms":["enhanced"],"dose":"18.78 mg silybin A + 35.5 mg silybin B (total silybin 54.28 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin A","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"2121.33","variance":"± 69.98 (SD)","units":"µg h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"silymarin (Indena milk thistle dry extract, 83% w/w silybin) in solid self-emulsifying pellets (Indena extract)","forms":["enhanced"],"dose":"18.78 mg silybin A + 35.5 mg silybin B (total silybin 54.28 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin A","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"2710.21","variance":"± 258.69 (SD)","units":"µg min/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"milk thistle dry extract in 0.9% NaCl solution (Indena extract)","forms":["silymarin"],"dose":"25.41 mg silybin A + 28.66 mg silybin B (total silybin 54.07 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin B","matrix":"plasma","parameter":"Tmax","detail":"t_max","value":"30","variance":"± 0 (SD)","units":"min","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"milk thistle dry extract in 0.9% NaCl solution (Indena extract)","forms":["silymarin"],"dose":"25.41 mg silybin A + 28.66 mg silybin B (total silybin 54.07 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.3405","variance":"± 0.0253 (SD)","units":"µg/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"milk thistle dry extract in 0.9% NaCl solution (Indena extract)","forms":["silymarin"],"dose":"25.41 mg silybin A + 28.66 mg silybin B (total silybin 54.07 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin B","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"12.70","variance":"± 0.67 (SD)","units":"µg h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"milk thistle dry extract in 0.9% NaCl solution (Indena extract)","forms":["silymarin"],"dose":"25.41 mg silybin A + 28.66 mg silybin B (total silybin 54.07 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin B","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"12.97","variance":"± 0.72 (SD)","units":"µg min/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"silymarin (Indena milk thistle dry extract, 83% w/w silybin) in solid self-emulsifying pellets (Indena extract)","forms":["enhanced"],"dose":"18.78 mg silybin A + 35.5 mg silybin B (total silybin 54.28 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin B","matrix":"plasma","parameter":"Tmax","detail":"t_max","value":"150","variance":"± 0 (SD)","units":"min","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"silymarin (Indena milk thistle dry extract, 83% w/w silybin) in solid self-emulsifying pellets (Indena extract)","forms":["enhanced"],"dose":"18.78 mg silybin A + 35.5 mg silybin B (total silybin 54.28 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"17.4333","variance":"± 0.7910 (SD)","units":"µg/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"silymarin (Indena milk thistle dry extract, 83% w/w silybin) in solid self-emulsifying pellets (Indena extract)","forms":["enhanced"],"dose":"18.78 mg silybin A + 35.5 mg silybin B (total silybin 54.28 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin B","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"1636.10","variance":"± 72.45 (SD)","units":"µg h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"silymarin (Indena milk thistle dry extract, 83% w/w silybin) in solid self-emulsifying pellets (Indena extract)","forms":["enhanced"],"dose":"18.78 mg silybin A + 35.5 mg silybin B (total silybin 54.28 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"Silybin B","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"2109.69","variance":"± 89.73 (SD)","units":"µg min/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Duodenal administration to fed rats; Table 3 header: mean ± S.D., n = 4"},{"pmid":"21111585","species":"rodent","arm":"","form":"silymarin (Indena milk thistle dry extract, 83% w/w silybin) in solid self-emulsifying pellets (Indena extract)","forms":["enhanced"],"dose":"18.78 mg silybin A + 35.5 mg silybin B (total silybin 54.28 mg) mg","doseBasis":"active compound","fed":"fed","n":"4","analyte":"silybin A","matrix":"plasma","parameter":"relative_bioavailability","detail":"fold-increase, pellets vs dry extract (AUC, dose-normalised per Eq. 2)","value":"354","variance":"","units":"times (fold)","location":"Results p.509","quote":"Bioavailabilities of silybin A and silybin B were 354 and 131 times respectively higher when administered as pellets compared to dry extract.","quoteCheck":"supported","note":"Stated in text only; not given as a table row"},{"pmid":"21111585","species":"rodent","arm":"","form":"silymarin (Indena milk thistle dry extract, 83% w/w silybin) in solid self-emulsifying pellets (Indena 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6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21549187","species":"rodent","arm":"","form":"o/w nanoemulsion: 5% Sefsol 218, 35% Smix (Tween 80:ethanol 2:1), 60% water","forms":["enhanced"],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"31.168","variance":"± 7.56 (SD)","units":"µg/mL","location":"Table 6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21549187","species":"rodent","arm":"","form":"o/w nanoemulsion: 5% Sefsol 218, 35% Smix (Tween 80:ethanol 2:1), 60% water","forms":["enhanced"],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"199.45","variance":"± 56.07 (SD)","units":"µg h/mL","location":"Table 6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21549187","species":"rodent","arm":"","form":"marketed silymarin suspension (SILYBON (Microlabs, Bangalore))","forms":["silymarin"],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.0","variance":"± 1.48 (SD)","units":"h","location":"Table 6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21549187","species":"rodent","arm":"","form":"marketed silymarin suspension (SILYBON (Microlabs, Bangalore))","forms":["silymarin"],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"11.865","variance":"± 5.901 (SD)","units":"µg/mL","location":"Table 6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21549187","species":"rodent","arm":"","form":"marketed silymarin suspension (SILYBON (Microlabs, Bangalore))","forms":["silymarin"],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"101.012","variance":"± 89.11 (SD)","units":"µg h/mL","location":"Table 6","quote":"","quoteCheck":"no quote","note":"Text (p.251) prints AUC 101.01 ± 89.11 vs 101.012 in Table 6"},{"pmid":"21549187","species":"rodent","arm":"","form":"silymarin bulk drug suspended in 10% gum acacia (Ranbaxy silymarin)","forms":["silymarin"],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.0","variance":"± 1.16 (SD)","units":"h","location":"Table 6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21549187","species":"rodent","arm":"","form":"silymarin bulk drug suspended in 10% gum acacia (Ranbaxy silymarin)","forms":["silymarin"],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"5.243","variance":"± 1.83 (SD)","units":"µg/mL","location":"Table 6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21549187","species":"rodent","arm":"","form":"silymarin bulk drug suspended in 10% gum acacia (Ranbaxy silymarin)","forms":["silymarin"],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"49.588","variance":"± 4.34 (SD)","units":"µg h/mL","location":"Table 6","quote":"","quoteCheck":"no quote","note":"Text (p.251-252) prints AUC as 49.58 ± 4.34 for standard group vs 49.588 in Table 6"},{"pmid":"21802925","species":"rodent","arm":"","form":"dry extract (83% w/w silybin: 39% silybin A, 44% silybin B), aqueous suspension (Indena)","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.27","variance":"± 0.11 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"dry extract (83% w/w silybin: 39% silybin A, 44% silybin B), aqueous suspension (Indena)","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 footnote a: median value"},{"pmid":"21802925","species":"rodent","arm":"","form":"dry extract (83% w/w silybin: 39% silybin A, 44% silybin B), aqueous suspension (Indena)","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"0.18","variance":"± 0.05 (SD)","units":"ng h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"dry extract (83% w/w silybin: 39% silybin A, 44% silybin B), aqueous suspension (Indena)","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel = AUC(formulation)/AUC(dry extract); reference","value":"1","variance":"","units":"ratio (unitless)","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Reference value"},{"pmid":"21802925","species":"rodent","arm":"","form":"15% dry extract in 85% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"10.6","variance":"± 3.3 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"15% dry extract in 85% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 footnote a: median value"},{"pmid":"21802925","species":"rodent","arm":"","form":"15% dry extract in 85% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"16.2","variance":"± 2.9 (SD)","units":"ng h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"15% dry extract in 85% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel = AUC(formulation)/AUC(dry extract)","value":"90","variance":"± 28 (SD)","units":"ratio (unitless)","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"15% coground dry extract + 15% Ac-Di-Sol (1:1 coground) in 70% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"228","variance":"± 39 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"15% coground dry extract + 15% Ac-Di-Sol (1:1 coground) in 70% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"Tmax","detail":"","value":"4","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 footnote a: median value"},{"pmid":"21802925","species":"rodent","arm":"","form":"15% coground dry extract + 15% Ac-Di-Sol (1:1 coground) in 70% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"449","variance":"± 59 (SD)","units":"ng h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"15% coground dry extract + 15% Ac-Di-Sol (1:1 coground) in 70% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin A","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel = AUC(formulation)/AUC(dry extract)","value":"2503","variance":"± 714 (SD)","units":"ratio (unitless)","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Text (p.167) rounds to 90/140 (M1) and about 2500/1450 (M3)"},{"pmid":"21802925","species":"rodent","arm":"","form":"dry extract (83% w/w silybin: 39% silybin A, 44% silybin B), aqueous suspension (Indena)","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.34","variance":"± 0.11 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"dry extract (83% w/w silybin: 39% silybin A, 44% silybin B), aqueous suspension (Indena)","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 footnote a: median value"},{"pmid":"21802925","species":"rodent","arm":"","form":"dry extract (83% w/w silybin: 39% silybin A, 44% silybin B), aqueous suspension (Indena)","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"0.22","variance":"± 0.05 (SD)","units":"ng h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"dry extract (83% w/w silybin: 39% silybin A, 44% silybin B), aqueous suspension (Indena)","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel = AUC(formulation)/AUC(dry extract); reference","value":"1","variance":"","units":"ratio (unitless)","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Reference value"},{"pmid":"21802925","species":"rodent","arm":"","form":"15% dry extract in 85% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"21.6","variance":"± 4.0 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"15% dry extract in 85% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 footnote a: median value"},{"pmid":"21802925","species":"rodent","arm":"","form":"15% dry extract in 85% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"30.8","variance":"± 3.5 (SD)","units":"ng h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"15% dry extract in 85% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel = AUC(formulation)/AUC(dry extract)","value":"140","variance":"± 34 (SD)","units":"ratio (unitless)","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"15% coground dry extract + 15% Ac-Di-Sol (1:1 coground) in 70% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"125","variance":"± 25 (SD)","units":"ng/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"15% coground dry extract + 15% Ac-Di-Sol (1:1 coground) in 70% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"Tmax","detail":"","value":"3","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 footnote a: median value"},{"pmid":"21802925","species":"rodent","arm":"","form":"15% coground dry extract + 15% Ac-Di-Sol (1:1 coground) in 70% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"319","variance":"± 25 (SD)","units":"ng h/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21802925","species":"rodent","arm":"","form":"15% coground dry extract + 15% Ac-Di-Sol (1:1 coground) in 70% Gelucire 50/13, spray-congealed","forms":[],"dose":"145 mg/kg dry extract (56.55 mg/kg silybin A and 63.80 mg/kg silybin B) mg/kg","doseBasis":"salt/compound","fed":"fasted overnight","n":"5","analyte":"Silybin B","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel = AUC(formulation)/AUC(dry extract)","value":"1449","variance":"± 355 (SD)","units":"ratio (unitless)","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Text (p.167) rounds to 90/140 (M1) and about 2500/1450 (M3)"},{"pmid":"24039417","species":"rodent","arm":"","form":"Solid nanoparticles (silymarin/castor oil/PVP/Transcutol HP/Tween 80, 5/3/3/1.25/1.25) made by SPG membrane emulsification + spray drying; in hard gelatin capsules","forms":["enhanced"],"dose":"10 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silymarin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"AUC","detail":"AUC from zero to infinity","value":"185.34","variance":"± 25.22 (SD)","units":"h ⋅ μg/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"24039417","species":"rodent","arm":"","form":"Legalon hard capsule (70 mg silymarin per capsule per Introduction) (Legalon (Bukwang Pharmaceutical))","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silymarin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"AUC","detail":"AUC from zero to infinity","value":"145.18","variance":"± 14.49 (SD)","units":"h ⋅ μg/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"24039417","species":"rodent","arm":"","form":"Solid nanoparticles (silymarin/castor oil/PVP/Transcutol HP/Tween 80, 5/3/3/1.25/1.25) made by SPG membrane emulsification + spray drying; in hard gelatin capsules","forms":["enhanced"],"dose":"10 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silymarin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"Cmax","detail":"","value":"22.07","variance":"± 2.25 (SD)","units":"μg/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"24039417","species":"rodent","arm":"","form":"Legalon hard capsule (70 mg silymarin per capsule per Introduction) (Legalon (Bukwang Pharmaceutical))","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silymarin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"Cmax","detail":"","value":"15.36","variance":"± 2.25 (SD)","units":"μg/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"24039417","species":"rodent","arm":"","form":"Solid nanoparticles (silymarin/castor oil/PVP/Transcutol HP/Tween 80, 5/3/3/1.25/1.25) made by SPG membrane emulsification + spray drying; in hard gelatin capsules","forms":["enhanced"],"dose":"10 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silymarin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.9","variance":"± 0.26 (SD)","units":"hours","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Statistic printed as mean ± SD"},{"pmid":"24039417","species":"rodent","arm":"","form":"Legalon hard capsule (70 mg silymarin per capsule per Introduction) (Legalon (Bukwang Pharmaceutical))","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silymarin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.82","variance":"± 0.41 (SD)","units":"hours","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"24039417","species":"rodent","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silymarin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"relative_bioavailability","detail":"bioavailability of nanoparticles vs commercial product, 'about 1.3-fold higher'","value":"about 1.3","variance":"","units":"fold","location":"Results p.3341 / Abstract","quote":"the bioavailability of the drug achieved by the nanoparticles was about 1.3-fold higher than that of the commercial product","quoteCheck":"supported","note":"Printed as 'about 1.3-fold'; value_as_printed 'about 1.3'"},{"pmid":"24766208","species":"rodent","arm":"","form":"Legalon capsule (Legalon (Bukwang Pharm.))","forms":["silymarin"],"dose":"140 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"Cmax","detail":"","value":"16.74","variance":"± 1.63 (SD)","units":"µg/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"24766208","species":"rodent","arm":"","form":"silymarin/PVP/Tween 80 5/2.5/2.5 (w/w), spray-dried, in hard gelatin capsules","forms":["silymarin"],"dose":"140 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"Cmax","detail":"","value":"44.85","variance":"± 11.42 (SD)","units":"µg/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"24766208","species":"rodent","arm":"","form":"Legalon capsule (Legalon (Bukwang Pharm.))","forms":["silymarin"],"dose":"140 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.90","variance":"± 0.39 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"24766208","species":"rodent","arm":"","form":"silymarin/PVP/Tween 80 5/2.5/2.5 (w/w), spray-dried, in hard gelatin capsules","forms":["silymarin"],"dose":"140 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.46","variance":"± 0.29 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Not marked significant"},{"pmid":"24766208","species":"rodent","arm":"","form":"Legalon capsule (Legalon (Bukwang Pharm.))","forms":["silymarin"],"dose":"140 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"AUC","detail":"","value":"157.04","variance":"± 36.29 (SD)","units":"h µg/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"AUC interval not stated in Table 3"},{"pmid":"24766208","species":"rodent","arm":"","form":"silymarin/PVP/Tween 80 5/2.5/2.5 (w/w), spray-dried, in hard gelatin capsules","forms":["silymarin"],"dose":"140 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"AUC","detail":"","value":"366.49","variance":"± 93.62 (SD)","units":"h µg/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"AUC interval not stated in Table 3"},{"pmid":"24766208","species":"rodent","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silybin (total, after enzymatic deconjugation)","matrix":"plasma","parameter":"relative_bioavailability","detail":"AUC of SD about 3-fold that of commercial product (text)","value":"about 3","variance":"","units":"fold","location":"Results p.623 / Abstract / Conclusion","quote":"the AUC of drug from SD was about 3-fold higher than that from commercial product","quoteCheck":"supported","note":""},{"pmid":"25149982","species":"rodent","arm":"","form":"silymarin suspended in 0.25% w/v CMC (silymarin from Sigma)","forms":["silymarin"],"dose":"200 mg/kg","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin (average of silybin A and B peaks)","matrix":"plasma","parameter":"Cmax","detail":"","value":"136.52","variance":"± 20.54 (SEM)","units":"ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table title: silymarin (equivalent to silybin); values mean ± SEM of six animals"},{"pmid":"25149982","species":"rodent","arm":"","form":"lyophilized soy phosphatidylcholine:cholesterol (6:1 molar) liposomes, sucrose 5% cryoprotectant, in 0.25% CMC","forms":["enhanced"],"dose":"200 mg/kg","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin (average of silybin A and B peaks)","matrix":"plasma","parameter":"Cmax","detail":"","value":"716.40","variance":"± 42.85 (SEM)","units":"ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table title: silymarin (equivalent to silybin); values mean ± SEM of six animals"},{"pmid":"25149982","species":"rodent","arm":"","form":"silymarin suspended in 0.25% w/v CMC (silymarin from Sigma)","forms":["silymarin"],"dose":"200 mg/kg","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin (average of silybin A and B peaks)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.50","variance":"± 0.0 (SEM)","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table title: silymarin (equivalent to silybin); values mean ± SEM of six animals"},{"pmid":"25149982","species":"rodent","arm":"","form":"lyophilized soy phosphatidylcholine:cholesterol (6:1 molar) liposomes, sucrose 5% cryoprotectant, in 0.25% CMC","forms":["enhanced"],"dose":"200 mg/kg","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin (average of silybin A and B peaks)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.50","variance":"± 0 (SEM)","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table title: silymarin (equivalent to silybin); values mean ± SEM of six animals"},{"pmid":"25149982","species":"rodent","arm":"","form":"silymarin suspended in 0.25% w/v CMC (silymarin from Sigma)","forms":["silymarin"],"dose":"200 mg/kg","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin (average of silybin A and B peaks)","matrix":"plasma","parameter":"AUC","detail":"AUC0-2","value":"115.20","variance":"± 5.99 (SEM)","units":"h*ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table title: silymarin (equivalent to silybin); values mean ± SEM of six animals"},{"pmid":"25149982","species":"rodent","arm":"","form":"lyophilized soy phosphatidylcholine:cholesterol (6:1 molar) liposomes, sucrose 5% cryoprotectant, in 0.25% CMC","forms":["enhanced"],"dose":"200 mg/kg","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin (average of silybin A and B peaks)","matrix":"plasma","parameter":"AUC","detail":"AUC0-2","value":"436.35","variance":"± 21.59 (SEM)","units":"h*ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table title: silymarin (equivalent to silybin); values mean ± SEM of six animals"},{"pmid":"25149982","species":"rodent","arm":"","form":"silymarin suspended in 0.25% w/v CMC (silymarin from Sigma)","forms":["silymarin"],"dose":"200 mg/kg","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin (average of silybin A and B peaks)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"158.83","variance":"± 5.25 (SEM)","units":"h*ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table title: silymarin (equivalent to silybin); values mean ± SEM of six animals"},{"pmid":"25149982","species":"rodent","arm":"","form":"lyophilized soy phosphatidylcholine:cholesterol (6:1 molar) liposomes, sucrose 5% cryoprotectant, in 0.25% CMC","forms":["enhanced"],"dose":"200 mg/kg","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin (average of silybin A and B peaks)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"499.66","variance":"± 23.40 (SEM)","units":"h*ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table title: silymarin (equivalent to silybin); values mean ± SEM of six animals"},{"pmid":"25149982","species":"rodent","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silybin (average of silybin A and B peaks)","matrix":"plasma","parameter":"relative_bioavailability","detail":"bioavailability of liposomal formulation vs silymarin suspension (Abstract)","value":"three and half fold","variance":"","units":"fold","location":"Abstract","quote":"The liposomal formulation yielded a three and half fold higher bioavailability of silymarin as compared with silymarin suspension.","quoteCheck":"supported","note":""},{"pmid":"25375210","species":"rodent","arm":"","form":"silymarin dissolved in PEG 400 with 15% ethanol","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.75","variance":"± 0.69 (SEM)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"liposome (SPC 3%, cholesterol 0.5%, DSPE-PEG 5000 0.5%)","forms":["phytosome","enhanced"],"dose":"10 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.92","variance":"± 0.13 (SEM)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"ethosome (as liposome plus 20% ethanol)","forms":["enhanced"],"dose":"10 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.55","variance":"± 0.34 (SEM)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"aqueous suspension in water","forms":[],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.02","variance":"± 0.01 (SEM)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"liposome","forms":["enhanced"],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.11","variance":"± 0.01 (SEM)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5; footnote b: P < 0.05 vs silymarin"},{"pmid":"25375210","species":"rodent","arm":"","form":"ethosome","forms":[],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.08","variance":"± 0.02 (SEM)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5; footnote b: P < 0.05 vs silymarin"},{"pmid":"25375210","species":"rodent","arm":"","form":"aqueous suspension in water","forms":[],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Tmax","detail":"","value":"10.0","variance":"± 2.9 (SEM)","units":"min","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"liposome","forms":["enhanced"],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Tmax","detail":"","value":"13.0","variance":"± 2.0 (SEM)","units":"min","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"ethosome","forms":[],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Tmax","detail":"","value":"20.0","variance":"± 10.3 (SEM)","units":"min","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"silymarin dissolved in PEG 400 with 15% ethanol","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval not stated)","value":"12.9","variance":"± 3.5 (SEM)","units":"min·μg·mL−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"liposome (SPC 3%, cholesterol 0.5%, DSPE-PEG 5000 0.5%)","forms":["phytosome","enhanced"],"dose":"10 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval not stated)","value":"7.99","variance":"± 0.9 (SEM)","units":"min·μg·mL−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"ethosome (as liposome plus 20% ethanol)","forms":["enhanced"],"dose":"10 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval not stated)","value":"14.7","variance":"± 3.2 (SEM)","units":"min·μg·mL−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"aqueous suspension in water","forms":[],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval not stated)","value":"2.04","variance":"± 0.74 (SEM)","units":"min·μg·mL−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"liposome","forms":["enhanced"],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval not stated)","value":"15.2","variance":"± 6.5 (SEM)","units":"min·μg·mL−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5; footnote b: P < 0.05 vs silymarin"},{"pmid":"25375210","species":"rodent","arm":"","form":"ethosome","forms":[],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC (interval not stated)","value":"4.48","variance":"± 1.03 (SEM)","units":"min·μg·mL−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table footnote: mean ± SEM, n = 5"},{"pmid":"25375210","species":"rodent","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silibinin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability of LSM and ESM vs silymarin (text; wording 'decrease by')","value":"7.45 and 2.2","variance":"","units":"fold","location":"Results p.11663","quote":"caused their relative bioavailabilities to decrease by 7.45- and 2.2-fold compared to silymarin (free form), respectively","quoteCheck":"value not in quote","note":"Sentence says 'decrease', but context (higher AUC) implies increase; recorded as printed, direction unclear. 7.45 for LSM and 2.2 for ESM as printed."},{"pmid":"25375210","species":"rodent","arm":"","form":"liposome","forms":["enhanced"],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC as printed in text","value":"15.17","variance":"± 6.51 (SEM)","units":"min·μg·mL−1","location":"Results p.11663","quote":"AUC values of silymarin (free form), LSM, and ESM were found to be 2.04 ± 0.74, 15.17 ± 6.51, 4.48 ± 1.03 min·μg·mL−1","quoteCheck":"supported","note":"Text shows 15.17 ± 6.51; Table 2 shows 15.2 ± 6.5 (rounding)"},{"pmid":"25375210","species":"rodent","arm":"","form":"aqueous suspension in water","forms":[],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC as printed in text","value":"2.04","variance":"± 0.74 (SEM)","units":"min·μg·mL−1","location":"Results p.11663","quote":"2.04 ± 0.74, 15.17 ± 6.51, 4.48 ± 1.03 min·μg·mL−1","quoteCheck":"supported","note":"Same as Table 2"},{"pmid":"25375210","species":"rodent","arm":"","form":"ethosome","forms":[],"dose":"100 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC as printed in text","value":"4.48","variance":"± 1.03 (SEM)","units":"min·μg·mL−1","location":"Results p.11663","quote":"2.04 ± 0.74, 15.17 ± 6.51, 4.48 ± 1.03 min·μg·mL−1","quoteCheck":"supported","note":"Same as Table 2"},{"pmid":"25735668","species":"rodent","arm":"","form":"NLC, 223.73 ± 43.39 nm, entrapment 78.65 ± 2.2%","forms":[],"dose":"50 mg/kg","doseBasis":"NR","fed":"fasted 16-20 h before study","n":"6","analyte":"silymarin (silybin quantified by HPLC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"25.565","variance":"± 0.969 (SD)","units":"µg/ml","location":"Table 8","quote":"","quoteCheck":"no quote","note":"Methods 4.11: results expressed as mean ± SD; Table 8 gives ± only for Cmax"},{"pmid":"25735668","species":"rodent","arm":"","form":"plain silymarin suspension","forms":["silymarin"],"dose":"50 mg/kg","doseBasis":"NR","fed":"fasted 16-20 h before study","n":"6","analyte":"silymarin (silybin quantified by HPLC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"14.050","variance":"± 0.552 (SD)","units":"µg/ml","location":"Table 8","quote":"","quoteCheck":"no quote","note":"Methods 4.11: results expressed as mean ± SD; Table 8 gives ± only for Cmax"},{"pmid":"25735668","species":"rodent","arm":"","form":"NLC-1 with inhibitor in feed","forms":[],"dose":"50 mg/kg","doseBasis":"NR","fed":"fasted 16-20 h before study","n":"6","analyte":"silymarin (silybin quantified by HPLC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"5.008","variance":"± 0.011 (SD)","units":"µg/ml","location":"Table 8","quote":"","quoteCheck":"no quote","note":"Methods 4.11: results expressed as mean ± SD; Table 8 gives ± only for Cmax; Abstract prints this as '5.008 ± 0.011 mg/ml'"},{"pmid":"25735668","species":"rodent","arm":"","form":"NLC, 223.73 ± 43.39 nm, entrapment 78.65 ± 2.2%","forms":[],"dose":"50 mg/kg","doseBasis":"NR","fed":"fasted 16-20 h before study","n":"6","analyte":"silymarin (silybin quantified by HPLC)","matrix":"plasma","parameter":"Tmax","detail":"","value":"4","variance":"","units":"h","location":"Table 8","quote":"","quoteCheck":"no quote","note":"No variance printed"},{"pmid":"25735668","species":"rodent","arm":"","form":"plain silymarin suspension","forms":["silymarin"],"dose":"50 mg/kg","doseBasis":"NR","fed":"fasted 16-20 h before study","n":"6","analyte":"silymarin (silybin quantified by HPLC)","matrix":"plasma","parameter":"Tmax","detail":"","value":"4","variance":"","units":"h","location":"Table 8","quote":"","quoteCheck":"no quote","note":"No variance printed; Results text says suspension Cmax 'achieved after 5 h' (inconsistent with Table 8)"},{"pmid":"25735668","species":"rodent","arm":"","form":"NLC-1 with inhibitor in feed","forms":[],"dose":"50 mg/kg","doseBasis":"NR","fed":"fasted 16-20 h before study","n":"6","analyte":"silymarin (silybin quantified by HPLC)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2","variance":"","units":"h","location":"Table 8","quote":"","quoteCheck":"no quote","note":"No variance printed"},{"pmid":"25735668","species":"rodent","arm":"","form":"NLC, 223.73 ± 43.39 nm, entrapment 78.65 ± 2.2%","forms":[],"dose":"50 mg/kg","doseBasis":"NR","fed":"fasted 16-20 h before study","n":"6","analyte":"silymarin (silybin quantified by HPLC)","matrix":"plasma","parameter":"AUC","detail":"AUCtot","value":"395.911","variance":"","units":"µg/ml/h","location":"Table 8","quote":"","quoteCheck":"no quote","note":"No variance printed; AUC interval 'tot' not defined"},{"pmid":"25735668","species":"rodent","arm":"","form":"plain silymarin suspension","forms":["silymarin"],"dose":"50 mg/kg","doseBasis":"NR","fed":"fasted 16-20 h before study","n":"6","analyte":"silymarin (silybin quantified by HPLC)","matrix":"plasma","parameter":"AUC","detail":"AUCtot","value":"159.26","variance":"","units":"µg/ml/h","location":"Table 8","quote":"","quoteCheck":"no quote","note":"No variance printed"},{"pmid":"25735668","species":"rodent","arm":"","form":"NLC-1 with inhibitor in feed","forms":[],"dose":"50 mg/kg","doseBasis":"NR","fed":"fasted 16-20 h before study","n":"6","analyte":"silymarin (silybin quantified by HPLC)","matrix":"plasma","parameter":"AUC","detail":"AUCtot","value":"16.31","variance":"","units":"µg/ml/h","location":"Table 8","quote":"","quoteCheck":"no quote","note":"No variance printed"},{"pmid":"25735668","species":"rodent","arm":"","form":"NLC, 223.73 ± 43.39 nm, entrapment 78.65 ± 2.2%","forms":[],"dose":"50 mg/kg","doseBasis":"NR","fed":"fasted 16-20 h before study","n":"6","analyte":"silymarin (silybin quantified by HPLC)","matrix":"plasma","parameter":"Cmax","detail":"Cmax in Results text","value":"25.525","variance":"","units":"µg/ml","location":"Results 7.6.5 p.120","quote":"maximum plasma concentration of 25.525 mg/ml is achieved within Tmax of 4 h","quoteCheck":"supported","note":"Inconsistent with Table 8 (25.565) and Abstract (25.565); units printed as mg/ml in text layer (µ lost); not verified on image"},{"pmid":"25735668","species":"rodent","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silymarin (silybin quantified by HPLC)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Abstract: 'confirms 2-fold increase in relative bioavailability' (NLC vs suspension, based on Cmax)","value":"2-fold","variance":"","units":"fold","location":"Abstract","quote":"this confirms 2-fold increase in relative bioavailability","quoteCheck":"supported","note":""},{"pmid":"25848259","species":"rodent","arm":"","form":"aqueous suspension in 1% CMC sodium","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"7.54","variance":"± 0.79 (SD)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; Table 2 rows are normal (control) rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"aqueous suspension in 1% CMC sodium","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.33","variance":"± 0.29 (SD)","units":"hours","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; Table 2 rows are normal (control) rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"aqueous suspension in 1% CMC sodium","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0→∞","value":"99.97","variance":"± 7.73 (SD)","units":"μg⋅hour/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; Table 2 rows are normal (control) rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"PEG 400 solution","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"12.94","variance":"± 6.57 (SD)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; Table 2 rows are normal (control) rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"PEG 400 solution","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.67","variance":"± 1.21 (SD)","units":"hours","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; Table 2 rows are normal (control) rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"PEG 400 solution","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0→∞","value":"179.55","variance":"± 44.21 (SD)","units":"μg⋅hour/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; Table 2 rows are normal (control) rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"SNEDDS: Capmul GMO 10%, Tween 20/Cremophor RH40 (1:1) 37.5%, Transcutol HP 37.5%, silymarin 15% (w/w)","forms":["silymarin"],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"11.84","variance":"± 6.21 (SD)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; Table 2 rows are normal (control) rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"SNEDDS: Capmul GMO 10%, Tween 20/Cremophor RH40 (1:1) 37.5%, Transcutol HP 37.5%, silymarin 15% (w/w)","forms":["silymarin"],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.31","variance":"± 0.65 (SD)","units":"hours","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; Table 2 rows are normal (control) rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"SNEDDS: Capmul GMO 10%, Tween 20/Cremophor RH40 (1:1) 37.5%, Transcutol HP 37.5%, silymarin 15% (w/w)","forms":["silymarin"],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0→∞","value":"163.42","variance":"± 48.05 (SD)","units":"μg⋅hour/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; Table 2 rows are normal (control) rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"aqueous suspension in 1% CMC sodium","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"5.37","variance":"± 4.72 (SD)","units":"μg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; RYGB rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"aqueous suspension in 1% CMC sodium","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"4.71","variance":"± 2.50 (SD)","units":"hours","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; RYGB rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"aqueous suspension in 1% CMC sodium","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0→∞","value":"72.77","variance":"± 27.18 (SD)","units":"μg⋅hour/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; RYGB rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"PEG 400 solution","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"13.77","variance":"± 6.72 (SD)","units":"μg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; RYGB rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"PEG 400 solution","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.0","variance":"± 0 (SD)","units":"hours","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; RYGB rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"PEG 400 solution","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0→∞","value":"123.20","variance":"± 22.44 (SD)","units":"μg⋅hour/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; RYGB rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"SNEDDS as above","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"13.65","variance":"± 5.59 (SD)","units":"μg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; RYGB rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"SNEDDS as above","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.83","variance":"± 1.29 (SD)","units":"hours","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; RYGB rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"SNEDDS as above","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0→∞","value":"180.15","variance":"± 40.86 (SD)","units":"μg⋅hour/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table note: mean ± SD (n=5-10); table title states silibinin (144 mg/kg); no AUC interval beyond AUC0→∞ per Methods; RYGB rats"},{"pmid":"25848259","species":"rodent","arm":"","form":"SNEDDS as above","forms":[],"dose":"600 mg/kg","doseBasis":"active compound","fed":"NR","n":"5-10","analyte":"silibinin (total, after sulfatase/β-glucuronidase hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"peak silibinin level at 2-3 h post-dosing for PEG 400 and SNEDDS (range as printed)","value":"2–3","variance":"","units":"hours","location":"Results p.2407","quote":"The peak plasma silibinin level occurred at 2–3 hours post-dosing for PEG 400 and SNEDDS.","quoteCheck":"supported","note":"Applies to both R-PEG and R-SNEDDS"},{"pmid":"26152876","species":"rodent","arm":"","form":"silybin solution","forms":[],"dose":"3.8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC (IV; interval not stated)","value":"11.75","variance":"± 1.15 (SD)","units":"µg min ml⁻¹","location":"Table 2","quote":"","quoteCheck":"no quote","note":"AUC interval NR"},{"pmid":"26152876","species":"rodent","arm":"","form":"silybin emulsomes (trilaurin, soy PC, cholesterol, Tween 80)","forms":[],"dose":"3.8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC (IV; interval not stated)","value":"26.03","variance":"± 2.32 (SD)","units":"µg min ml⁻¹","location":"Table 2","quote":"","quoteCheck":"no quote","note":"AUC interval NR; * P < 0.05 vs SIL solution"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"total SLB (metabolized + non-metabolized)","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"39.8","variance":"± 3.41 (NR)","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; sparse-sampling NCA on pooled mean curve; printed unit '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"total SLB (metabolized + non-metabolized)","matrix":"serum","parameter":"Cmax","detail":"","value":"84.1","variance":"± 5.43 (NR)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; observed"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"total SLB (metabolized + non-metabolized)","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"42.5","variance":"","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"No %RSE printed; unit printed '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"total SLB (metabolized + non-metabolized)","matrix":"serum","parameter":"Tmax","detail":"","value":"0.083","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"SLB metabolite (calculated as total minus parent)","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"34.2","variance":"± 4.3 (NR)","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; sparse-sampling NCA on pooled mean curve; printed unit '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"SLB metabolite (calculated as total minus parent)","matrix":"serum","parameter":"Cmax","detail":"","value":"68.8","variance":"± 8.40 (NR)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; observed"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"SLB metabolite (calculated as total minus parent)","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"36.4","variance":"","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"No %RSE printed; unit printed '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"SLB metabolite (calculated as total minus parent)","matrix":"serum","parameter":"Tmax","detail":"","value":"0.083","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"parent (non-metabolized) SLB","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"5.42","variance":"± 8.02 (NR)","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; sparse-sampling NCA on pooled mean curve; printed unit '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"parent (non-metabolized) SLB","matrix":"serum","parameter":"Cmax","detail":"","value":"14.0","variance":"± 16.7 (NR)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; observed"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"parent (non-metabolized) SLB","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"6.10","variance":"","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"No %RSE printed; unit printed '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"0.5 mg per animal (abstract: 20 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"parent (non-metabolized) SLB","matrix":"serum","parameter":"Tmax","detail":"","value":"0.083","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"total SLB (metabolized + non-metabolized)","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"48.4","variance":"± 9.65 (NR)","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; sparse-sampling NCA on pooled mean curve; printed unit '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"total SLB (metabolized + non-metabolized)","matrix":"serum","parameter":"Cmax","detail":"","value":"62.6","variance":"± 16.5 (NR)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; observed"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"total SLB (metabolized + non-metabolized)","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"50.7","variance":"","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"No %RSE printed; unit printed '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"total SLB (metabolized + non-metabolized)","matrix":"serum","parameter":"Tmax","detail":"","value":"0.167","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"SLB metabolite (calculated as total minus parent)","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"46.5","variance":"± 10.4 (NR)","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; sparse-sampling NCA on pooled mean curve; printed unit '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"SLB metabolite (calculated as total minus parent)","matrix":"serum","parameter":"Cmax","detail":"","value":"57.5","variance":"± 15.6 (NR)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; observed"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"SLB metabolite (calculated as total minus parent)","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"48.7","variance":"","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"No %RSE printed; unit printed '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"SLB metabolite (calculated as total minus parent)","matrix":"serum","parameter":"Tmax","detail":"","value":"0.167","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"parent (non-metabolized) SLB","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"1.52","variance":"± 9.39 (NR)","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; sparse-sampling NCA on pooled mean curve; printed unit '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"parent (non-metabolized) SLB","matrix":"serum","parameter":"Cmax","detail":"","value":"5.08","variance":"± 30.9 (NR)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Value in parentheses in Table 3 is %RSE (relative standard error of sparse-sampling NCA estimate), not SD; observed"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"parent (non-metabolized) SLB","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"1.97","variance":"","units":"h µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"No %RSE printed; unit printed '(h µg)/mL'"},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"parent (non-metabolized) SLB","matrix":"serum","parameter":"Tmax","detail":"","value":"0.167","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26222744","species":"rodent","arm":"","form":"silibinin-hydroxypropyl-β-cyclodextrin lyophilized product reconstituted in water for injection","forms":[],"dose":"1.25 mg per animal (abstract: 50 mg/kg)","doseBasis":"active compound","fed":"NR","n":"30","analyte":"total SLB","matrix":"serum","parameter":"relative_bioavailability","detail":"SLB-HP-β-CD lyophilized product vs Siliphos (literature, rat), via author-calculated F","value":"0.9","variance":"","units":"fraction","location":"Discussion (p. 371)","quote":"SLB was found to be almost equally absorbed (F = 0.9) when administered as SLB-HP-β-CD lyophilized product and Siliphos","quoteCheck":"supported","note":"Author calculation using literature AUC from a different study/species; label 'F = 0.9' as printed"},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin powder suspended in purified water","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.417","variance":"± 0.204 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin powder suspended in purified water","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.640","variance":"± 0.132 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin powder suspended in purified water","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"3.824","variance":"± 0.355 (SD)","units":"µg/mL h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"last time point NR; unit printed as 'µg/mL h'"},{"pmid":"26543366","species":"rodent","arm":"","form":"Yiganling tablets dispersed in distilled water","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.916","variance":"± 0.129 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26543366","species":"rodent","arm":"","form":"Yiganling tablets dispersed in distilled water","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.703","variance":"± 0.072 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26543366","species":"rodent","arm":"","form":"Yiganling tablets dispersed in distilled water","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"7.753","variance":"± 0.576 (SD)","units":"µg/mL h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"* P<0.05 vs SM powder; last time point NR; unit printed as 'µg/mL h'"},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin liposomes containing sodium glycocholate, prepared by supercritical-fluid SEDS","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"7.667","variance":"± 0.816 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"* P<0.05 vs SM powder"},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin liposomes containing sodium glycocholate, prepared by supercritical-fluid SEDS","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.296","variance":"± 0.137 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"* P<0.05 vs SM powder"},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin liposomes containing sodium glycocholate, prepared by supercritical-fluid SEDS","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"18.406","variance":"± 1.481 (SD)","units":"µg/mL h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"* P<0.05 vs SM powder; last time point NR; unit printed as 'µg/mL h'"},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin liposomes containing sodium glycocholate, reversed-phase evaporation","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"5.667","variance":"± 0.816 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"* P<0.05 vs SM powder"},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin liposomes containing sodium glycocholate, reversed-phase evaporation","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.162","variance":"± 0.103 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"* P<0.05 vs SM powder"},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin liposomes containing sodium glycocholate, reversed-phase evaporation","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"15.331","variance":"± 2.181 (SD)","units":"µg/mL h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"* P<0.05 vs SM powder; last time point NR; unit printed as 'µg/mL h'"},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin liposomes containing sodium glycocholate, thin-film dispersion","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"5.500","variance":"± 1.225 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"* P<0.05 vs SM powder"},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin liposomes containing sodium glycocholate, thin-film dispersion","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.931","variance":"± 0.115 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"* P<0.05 vs SM powder"},{"pmid":"26543366","species":"rodent","arm":"","form":"silymarin liposomes containing sodium glycocholate, thin-film dispersion","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silymarin (measured as silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"14.054","variance":"± 1.417 (SD)","units":"µg/mL h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"* P<0.05 vs SM powder; last time point NR; unit printed as 'µg/mL h'"},{"pmid":"26556526","species":"rodent","arm":"","form":"silybin dispersed in 0.5% Tween 80 + 0.3% HPMC","forms":[],"dose":"30 mg/kg","doseBasis":"active compound","fed":"NR (SPIP rats fasted 12 h; PK rats not stated)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.418","variance":"± 0.051 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26556526","species":"rodent","arm":"","form":"silybin dispersed in 0.5% Tween 80 + 0.3% HPMC","forms":[],"dose":"30 mg/kg","doseBasis":"active compound","fed":"NR (SPIP rats fasted 12 h; PK rats not stated)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.17","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"No variance printed for tmax; statistic type not named"},{"pmid":"26556526","species":"rodent","arm":"","form":"silybin dispersed in 0.5% Tween 80 + 0.3% HPMC","forms":[],"dose":"30 mg/kg","doseBasis":"active compound","fed":"NR (SPIP rats fasted 12 h; PK rats not stated)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"1.011","variance":"± 0.203 (SD)","units":"µg h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"last time point NR (sampling to 12 h); unit printed 'µg h/mL'"},{"pmid":"26556526","species":"rodent","arm":"","form":"hyaluronic acid-adipic dihydrazide-deoxycholic acid (DS 10%) polymeric micelles loaded with silybin","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.885","variance":"± 0.145 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"** p<0.01 vs suspension"},{"pmid":"26556526","species":"rodent","arm":"","form":"hyaluronic acid-adipic dihydrazide-deoxycholic acid (DS 10%) polymeric micelles loaded with silybin","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.0","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"No variance printed for tmax; statistic type not named"},{"pmid":"26556526","species":"rodent","arm":"","form":"hyaluronic acid-adipic dihydrazide-deoxycholic acid (DS 10%) polymeric micelles loaded with silybin","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"4.429","variance":"± 0.682 (SD)","units":"µg h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"** p<0.01 vs suspension; last time point NR (sampling to 12 h); unit printed 'µg h/mL'"},{"pmid":"26556526","species":"rodent","arm":"","form":"hyaluronic acid-adipic dihydrazide-glycyrrhetinic acid (DS 20%) polymeric micelles loaded with silybin","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.879","variance":"± 0.132 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"** p<0.01 vs suspension"},{"pmid":"26556526","species":"rodent","arm":"","form":"hyaluronic acid-adipic dihydrazide-glycyrrhetinic acid (DS 20%) polymeric micelles loaded with silybin","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"No variance printed for tmax; statistic type not named"},{"pmid":"26556526","species":"rodent","arm":"","form":"hyaluronic acid-adipic dihydrazide-glycyrrhetinic acid (DS 20%) polymeric micelles loaded with silybin","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"4.074","variance":"± 0.657 (SD)","units":"µg h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"** p<0.01 vs suspension; last time point NR (sampling to 12 h); unit printed 'µg h/mL'"},{"pmid":"26770331","species":"rodent","arm":"","form":"silybin suspension (silybin from Sigma-Aldrich)","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t (0-24 h)","value":"5342","variance":"","units":"ng/ml.h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26770331","species":"rodent","arm":"","form":"PLGA nanoparticles loaded with silybin (optimized: PLGA 10 mg, PVA 2000, PET width 6; EE 88%, 223 nm, zeta -25 mV)","forms":["enhanced"],"dose":"12 mg/kg (silybin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t (0-24 h)","value":"132122","variance":"","units":"ng/ml.h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26770331","species":"rodent","arm":"","form":"silybin suspension (silybin from Sigma-Aldrich)","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"plasma","parameter":"Cmax","detail":"","value":"10120","variance":"± 523 (NR)","units":"ng/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Variance printed after ± with no type stated. Conflicts with Cmax 134.2 ng/mL in Results text p.17415."},{"pmid":"26770331","species":"rodent","arm":"","form":"PLGA nanoparticles loaded with silybin (optimized: PLGA 10 mg, PVA 2000, PET width 6; EE 88%, 223 nm, zeta -25 mV)","forms":["enhanced"],"dose":"12 mg/kg (silybin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"plasma","parameter":"Cmax","detail":"","value":"52220","variance":"± 526 (NR)","units":"ng/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Variance printed after ± with no type stated. Conflicts with Cmax 182.4 ng/mL in Results text p.17415."},{"pmid":"26770331","species":"rodent","arm":"","form":"silybin suspension (silybin from Sigma-Aldrich)","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"plasma","parameter":"Cmax","detail":"text value","value":"134.2","variance":"","units":"ng/mL","location":"Results p.17415 (Pharmacokinetics section)","quote":"silybin suspension was quickly retained through the rat gastrointestinal tract with a Cmax of 134.2 ng/mL at a Tmax of 10 minutes","quoteCheck":"supported","note":"Inconsistent with Table 3 (10120 ng/ml)."},{"pmid":"26770331","species":"rodent","arm":"","form":"silybin suspension (silybin from Sigma-Aldrich)","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"plasma","parameter":"Tmax","detail":"text value","value":"10","variance":"","units":"minutes","location":"Results p.17415","quote":"Cmax of 134.2 ng/mL at a Tmax of 10 minutes","quoteCheck":"supported","note":"Inconsistent with Table 3 where Tmax is given only for tumor."},{"pmid":"26770331","species":"rodent","arm":"","form":"PLGA nanoparticles loaded with silybin (optimized: PLGA 10 mg, PVA 2000, PET width 6; EE 88%, 223 nm, zeta -25 mV)","forms":["enhanced"],"dose":"12 mg/kg (silybin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"plasma","parameter":"Cmax","detail":"text value","value":"182.4","variance":"","units":"ng/mL","location":"Results p.17415","quote":"nanoparticles accomplished a Cmax of 182.4 ng/mL at a Tmax of 15 minutes","quoteCheck":"supported","note":"Inconsistent with Table 3 (52220 ng/ml)."},{"pmid":"26770331","species":"rodent","arm":"","form":"PLGA nanoparticles loaded with silybin (optimized: PLGA 10 mg, PVA 2000, PET width 6; EE 88%, 223 nm, zeta -25 mV)","forms":["enhanced"],"dose":"12 mg/kg (silybin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"plasma","parameter":"Tmax","detail":"text value","value":"15","variance":"","units":"minutes","location":"Results p.17415","quote":"Cmax of 182.4 ng/mL at a Tmax of 15 minutes","quoteCheck":"supported","note":""},{"pmid":"26770331","species":"rodent","arm":"","form":"PLGA nanoparticles loaded with silybin (optimized: PLGA 10 mg, PVA 2000, PET width 6; EE 88%, 223 nm, zeta -25 mV)","forms":["enhanced"],"dose":"12 mg/kg (silybin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"plasma","parameter":"relative_bioavailability","detail":"based on AUC0-inf, nanoparticle vs suspension","value":"178","variance":"","units":"%","location":"Results p.17415","quote":"oral bioavailability of silybin nanoparticle was around 178% as contrasted at that of silybin suspension","quoteCheck":"supported","note":"Printed as 'around 178%'."},{"pmid":"26770331","species":"rodent","arm":"","form":"silybin suspension (silybin from Sigma-Aldrich)","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"tumor","parameter":"AUC","detail":"AUC0-t (0-168 h)","value":"212612","variance":"","units":"ng/ml.h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26770331","species":"rodent","arm":"","form":"silybin suspension (silybin from Sigma-Aldrich)","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"tumor","parameter":"Tmax","detail":"","value":"1","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26770331","species":"rodent","arm":"","form":"PLGA nanoparticles loaded with silybin (optimized: PLGA 10 mg, PVA 2000, PET width 6; EE 88%, 223 nm, zeta -25 mV)","forms":["enhanced"],"dose":"12 mg/kg (silybin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"tumor","parameter":"AUC","detail":"AUC0-t (0-168 h)","value":"322848","variance":"","units":"ng/ml.h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26770331","species":"rodent","arm":"","form":"PLGA nanoparticles loaded with silybin (optimized: PLGA 10 mg, PVA 2000, PET width 6; EE 88%, 223 nm, zeta -25 mV)","forms":["enhanced"],"dose":"12 mg/kg (silybin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"tumor","parameter":"Tmax","detail":"","value":"1","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26770331","species":"rodent","arm":"","form":"silybin suspension (silybin from Sigma-Aldrich)","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"lung","parameter":"AUC","detail":"AUC0-t (0-72 h)","value":"12224","variance":"","units":"ng/ml.h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26770331","species":"rodent","arm":"","form":"PLGA nanoparticles loaded with silybin (optimized: PLGA 10 mg, PVA 2000, PET width 6; EE 88%, 223 nm, zeta -25 mV)","forms":["enhanced"],"dose":"12 mg/kg (silybin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"12","analyte":"silybin (total, encapsulated + released)","matrix":"lung","parameter":"AUC","detail":"AUC0-t (0-72 h)","value":"38422","variance":"","units":"ng/ml.h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"27436270","species":"rodent","arm":"","form":"silibinin:PVP 1:1 w/w nanoparticles by nanoemulsification, lyophilised (166.1±5.5 nm, EE 97.50%±0.01%)","forms":["enhanced"],"dose":"100 mg/kg silibinin equivalent","doseBasis":"active compound","fed":"NR","n":"8","analyte":"free silibinin","matrix":"serum","parameter":"Tmax","detail":"time of peak serum level (text, no numeric Cmax given)","value":"2","variance":"","units":"hours","location":"Results p.1858 (High bioavailability of SB-NP)","quote":"SB-NP displayed higher serum levels of free silibinin, which peaked at 2 hours following oral administration","quoteCheck":"supported","note":"Text gives peak time for SB-NP only; Tmax for SB not stated."},{"pmid":"27575878","species":"rodent","arm":"","form":"silybin coarse powder (purity >95%)","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight (12 h)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"202.3","variance":"± 18.7 (SD)","units":"ng·mL−1·h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"27575878","species":"rodent","arm":"","form":"silybin coarse powder (purity >95%)","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight (12 h)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"tmax","value":"3.0","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 footnotes: * P<0.05 and ** P<0.01 vs the SN (silybin) group; *** P<0.05 and a P<0.01 vs the SN-NCS group. Tmax printed without variance."},{"pmid":"27575878","species":"rodent","arm":"","form":"silybin coarse powder (purity >95%)","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight (12 h)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"51.4","variance":"± 10.1 (SD)","units":"ng·mL−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"27575878","species":"rodent","arm":"","form":"silybin nanocrystals (~300-340 nm) by high-pressure homogenization","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight (12 h)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"508.1","variance":"± 47.1 (SD)","units":"ng·mL−1·h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"27575878","species":"rodent","arm":"","form":"silybin nanocrystals (~300-340 nm) by high-pressure homogenization","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight (12 h)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"tmax","value":"6.0","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 footnotes: * P<0.05 and ** P<0.01 vs the SN (silybin) group; *** P<0.05 and a P<0.01 vs the SN-NCS group. Tmax printed without variance."},{"pmid":"27575878","species":"rodent","arm":"","form":"silybin nanocrystals (~300-340 nm) by high-pressure homogenization","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight (12 h)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"73.8","variance":"± 4.5 (SD)","units":"ng·mL−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"27575878","species":"rodent","arm":"","form":"silybin nanocrystals adsorbed on droplets of glyceryl monocaprylate (Capmul MCM C8) oil; prepared at 100 MPa","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight (12 h)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"812.7","variance":"± 25.1 (SD)","units":"ng·mL−1·h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"27575878","species":"rodent","arm":"","form":"silybin nanocrystals adsorbed on droplets of glyceryl monocaprylate (Capmul MCM C8) oil; prepared at 100 MPa","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight (12 h)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"tmax","value":"5.0","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 footnotes: * P<0.05 and ** P<0.01 vs the SN (silybin) group; *** P<0.05 and a P<0.01 vs the SN-NCS group. Tmax printed without variance."},{"pmid":"27575878","species":"rodent","arm":"","form":"silybin nanocrystals adsorbed on droplets of glyceryl monocaprylate (Capmul MCM C8) oil; prepared at 100 MPa","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight (12 h)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"184.9","variance":"± 8.2 (SD)","units":"ng·mL−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"28503949","species":"rodent","arm":"","form":"silymarin standard suspension (silymarin from Sigma-Aldrich)","forms":["silymarin"],"dose":"42 mg/kg","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin (HPTLC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"5.24","variance":"± 4.31 (SD)","units":"µg/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Units printed as 'lg' in text layer; page image shows µg. Table title gives n = 6, footnote gives n = 3. Tmax given as mean ± SD."},{"pmid":"28503949","species":"rodent","arm":"","form":"silymarin standard suspension (silymarin from Sigma-Aldrich)","forms":["silymarin"],"dose":"42 mg/kg","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin (HPTLC)","matrix":"plasma","parameter":"Tmax","detail":"","value":"3.0","variance":"± 0.31 (SD)","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Units printed as 'lg' in text layer; page image shows µg. Table title gives n = 6, footnote gives n = 3. Tmax given as mean ± SD."},{"pmid":"28503949","species":"rodent","arm":"","form":"silymarin standard suspension (silymarin from Sigma-Aldrich)","forms":["silymarin"],"dose":"42 mg/kg","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin (HPTLC)","matrix":"plasma","parameter":"AUC","detail":"AUC0-all","value":"17.82","variance":"± 7.32 (SD)","units":"µg h/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Units printed as 'lg' in text layer; page image shows µg. Table title gives n = 6, footnote gives n = 3. Tmax given as mean ± SD."},{"pmid":"28503949","species":"rodent","arm":"","form":"conventional silymarin formulation (marketed Limarin suspension) (Limarin)","forms":["silymarin"],"dose":"35 mg/kg","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin (HPTLC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"10.36","variance":"± 1.06 (SD)","units":"µg/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Units printed as 'lg' in text layer; page image shows µg. Table title gives n = 6, footnote gives n = 3. Tmax given as mean ± SD."},{"pmid":"28503949","species":"rodent","arm":"","form":"conventional silymarin formulation (marketed Limarin suspension) (Limarin)","forms":["silymarin"],"dose":"35 mg/kg","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin (HPTLC)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.0","variance":"± 0.62 (SD)","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Units printed as 'lg' in text layer; page image shows µg. Table title gives n = 6, footnote gives n = 3. Tmax given as mean ± SD."},{"pmid":"28503949","species":"rodent","arm":"","form":"conventional silymarin formulation (marketed Limarin suspension) (Limarin)","forms":["silymarin"],"dose":"35 mg/kg","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin (HPTLC)","matrix":"plasma","parameter":"AUC","detail":"AUC0-all","value":"37.43","variance":"± 2.89 (SD)","units":"µg h/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Units printed as 'lg' in text layer; page image shows µg. Table title gives n = 6, footnote gives n = 3. Tmax given as mean ± SD."},{"pmid":"28503949","species":"rodent","arm":"","form":"optimized nanoemulsion: Sefsol 218 5.8% v/v, Smix (Kolliphor RH40:PEG 400, 2:1) 28.99% v/v, water 65.22% v/v; droplet 21.24 nm","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin (HPTLC)","matrix":"plasma","parameter":"Cmax","detail":"","value":"38.62","variance":"± 2.43 (SD)","units":"µg/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Units printed as 'lg' in text layer; page image shows µg. Table title gives n = 6, footnote gives n = 3. Tmax given as mean ± SD."},{"pmid":"28503949","species":"rodent","arm":"","form":"optimized nanoemulsion: Sefsol 218 5.8% v/v, Smix (Kolliphor RH40:PEG 400, 2:1) 28.99% v/v, water 65.22% v/v; droplet 21.24 nm","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin (HPTLC)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"± 0.45 (SD)","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Units printed as 'lg' in text layer; page image shows µg. Table title gives n = 6, footnote gives n = 3. Tmax given as mean ± SD."},{"pmid":"28503949","species":"rodent","arm":"","form":"optimized nanoemulsion: Sefsol 218 5.8% v/v, Smix (Kolliphor RH40:PEG 400, 2:1) 28.99% v/v, water 65.22% v/v; droplet 21.24 nm","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin (HPTLC)","matrix":"plasma","parameter":"AUC","detail":"AUC0-all","value":"308.51","variance":"± 4.23 (SD)","units":"µg h/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Units printed as 'lg' in text layer; page image shows µg. Table title gives n = 6, footnote gives n = 3. Tmax given as mean ± SD."},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin solid dispersion pellets","forms":["enhanced"],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.41","variance":"± 0.43 (NR)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin solid dispersion pellets","forms":["enhanced"],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.00","variance":"± 0.84 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin solid dispersion pellets","forms":["enhanced"],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-12","value":"4.74","variance":"± 1.12 (NR)","units":"μg·h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin solid dispersion pellets","forms":["enhanced"],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"4.81","variance":"± 1.09 (NR)","units":"μg·h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin solid dispersion pellets","forms":["enhanced"],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"RBA % vs fast-release SB pellets","value":"100","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-hexanoyl (6C) lipid conjugate in solid lipid nanoparticles (Precirol ATO 5, Tween 80)","forms":["enhanced"],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"18.68","variance":"± 4.01 (NR)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-hexanoyl (6C) lipid conjugate in solid lipid nanoparticles (Precirol ATO 5, Tween 80)","forms":["enhanced"],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.25","variance":"± 0.00 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-hexanoyl (6C) lipid conjugate in solid lipid nanoparticles (Precirol ATO 5, Tween 80)","forms":["enhanced"],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-12","value":"27.85","variance":"± 4.59 (NR)","units":"μg·h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-hexanoyl (6C) lipid conjugate in solid lipid nanoparticles (Precirol ATO 5, Tween 80)","forms":["enhanced"],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"28.10","variance":"± 4.56 (NR)","units":"μg·h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-hexanoyl (6C) lipid conjugate in solid lipid nanoparticles (Precirol ATO 5, Tween 80)","forms":["enhanced"],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"RBA % vs fast-release SB pellets","value":"587.47","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-lauroyl (12C) lipid conjugate in SLNs","forms":[],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"15.24","variance":"± 3.14 (NR)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-lauroyl (12C) lipid conjugate in SLNs","forms":[],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.46","variance":"± 0.10 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '***' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-lauroyl (12C) lipid conjugate in SLNs","forms":[],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-12","value":"32.18","variance":"± 5.26 (NR)","units":"μg·h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-lauroyl (12C) lipid conjugate in SLNs","forms":[],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"32.39","variance":"± 5.20 (NR)","units":"μg·h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-lauroyl (12C) lipid conjugate in SLNs","forms":[],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"RBA % vs fast-release SB pellets","value":"678.69","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-stearoyl (18C) lipid conjugate in SLNs","forms":[],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"6.87","variance":"± 0.82 (NR)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '**' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-stearoyl (18C) lipid conjugate in SLNs","forms":[],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.92","variance":"± 0.66 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-stearoyl (18C) lipid conjugate in SLNs","forms":[],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-12","value":"24.37","variance":"± 4.16 (NR)","units":"μg·h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-stearoyl (18C) lipid conjugate in SLNs","forms":[],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"24.58","variance":"± 4.32 (NR)","units":"μg·h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28778838","species":"rodent","arm":"","form":"silybin-stearoyl (18C) lipid conjugate in SLNs","forms":[],"dose":"9 mg/kg SB equivalent","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"RBA % vs fast-release SB pellets","value":"514.05","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table lists '****' significance marker vs pellets"},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"parent (non-metabolized) silibinin","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"450.2","variance":"± 5.8 (% relative standard error) (NR)","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"parent (non-metabolized) silibinin","matrix":"serum","parameter":"Cmax","detail":"","value":"6.11","variance":"± 16.3 (% relative standard error) (NR)","units":"µg/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"parent (non-metabolized) silibinin","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"652","variance":"","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"parent (non-metabolized) silibinin","matrix":"serum","parameter":"Tmax","detail":"","value":"15","variance":"","units":"min","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"total silibinin (parent + metabolized)","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"1180.2","variance":"± 4.3 (% relative standard error) (NR)","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"total silibinin (parent + metabolized)","matrix":"serum","parameter":"Cmax","detail":"","value":"18.4","variance":"± 7.7 (% relative standard error) (NR)","units":"µg/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"total silibinin (parent + metabolized)","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"1318","variance":"","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"total silibinin (parent + metabolized)","matrix":"serum","parameter":"Tmax","detail":"","value":"15","variance":"","units":"min","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"metabolized silibinin","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"781.8","variance":"± 9.1 (% relative standard error) (NR)","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"metabolized silibinin","matrix":"serum","parameter":"Cmax","detail":"","value":"12.3","variance":"± 8.6 (% relative standard error) (NR)","units":"µg/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"metabolized silibinin","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"813","variance":"","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-HP-β-CD complex","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"28","analyte":"metabolized silibinin","matrix":"serum","parameter":"Tmax","detail":"","value":"15","variance":"","units":"min","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"parent (non-metabolized) silibinin","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"957.9","variance":"± 17.6 (% relative standard error) (NR)","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve. Table marks '*': footnote gives AUC0-t = 847.7 (20.7) excluding 5 min sample"},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"parent (non-metabolized) silibinin","matrix":"serum","parameter":"Cmax","detail":"","value":"24.0","variance":"± 30.2 (% relative standard error) (NR)","units":"µg/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"parent (non-metabolized) silibinin","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"966.2","variance":"","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve. Table marks '*': footnote AUCinf = 856.0 excluding 5 min sample"},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"parent (non-metabolized) silibinin","matrix":"serum","parameter":"Tmax","detail":"","value":"30","variance":"","units":"min","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"total silibinin (parent + metabolized)","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"2223.14","variance":"± 9.9 (% relative standard error) (NR)","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve. Table marks '**': footnote AUC0-t = 1938.2 (11.0) excluding 5 min sample"},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"total silibinin (parent + metabolized)","matrix":"serum","parameter":"Cmax","detail":"","value":"34.14","variance":"± 23.8 (% relative standard error) (NR)","units":"µg/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve. Table marks '**': footnote Cmax = 26.9 (13.8) ug/mL for Tmax = 15 min excluding 5 min sample"},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"total silibinin (parent + metabolized)","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"2229.7","variance":"","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve. Table marks '**': footnote AUCinf = 1944.6 excluding 5 min sample"},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"total silibinin (parent + metabolized)","matrix":"serum","parameter":"Tmax","detail":"","value":"5","variance":"","units":"min","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"metabolized silibinin","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"1331.9","variance":"± 9.48 (% relative standard error) (NR)","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve. Table marks '#': footnote AUC0-t = 1209.5 (9.9) excluding 5 min sample"},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"metabolized silibinin","matrix":"serum","parameter":"Cmax","detail":"","value":"15.0","variance":"± 40.7 (% relative standard error) (NR)","units":"µg/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve. Table marks '#': footnote Cmax = 12.6 (21.5) ug/mL for Tmax = 15 min excluding 5 min sample"},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"metabolized silibinin","matrix":"serum","parameter":"AUC","detail":"AUCinf","value":"1379.1","variance":"","units":"(min × µg)/mL","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28952834","species":"rodent","arm":"","form":"lyophilized silibinin-hydroxypropyl-β-cyclodextrin complex (1:2 molar), reconstituted in water","forms":[],"dose":"2.5 mg/kg IV","doseBasis":"active compound","fed":"NR","n":"10","analyte":"metabolized silibinin","matrix":"serum","parameter":"Tmax","detail":"","value":"5","variance":"","units":"min","location":"Table 1 (serum)","quote":"","quoteCheck":"no quote","note":"NCA of sparse-sampling mean concentration curve."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"free silybin A (SBa)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"1098","variance":"± 416 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"free silybin B (SBb)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"992.3","variance":"± 287 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"free silybin A (SBa)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"1970","variance":"± 330 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. Significance marker '**' vs silybin alone."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"free silybin B (SBb)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"1463","variance":"± 168 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. Significance marker '**' vs silybin alone."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"free silybin A (SBa)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"1443","variance":"± 518 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"free silybin B (SBb)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"1019","variance":"± 1127 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. SD (1127) exceeds the mean as printed."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"free silybin A (SBa)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"2087","variance":"± 352 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. Significance marker '*' vs silybin alone."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"free silybin B (SBb)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"1518","variance":"± 151 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. Significance marker '**' vs silybin alone."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"free silybin A (SBa)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.50","variance":"± 0.00 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"free silybin B (SBb)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.50","variance":"± 0.00 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"free silybin A (SBa)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.33","variance":"± 0.26 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"free silybin B (SBb)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.42","variance":"± 0.20 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"free silybin A (SBa)","matrix":"plasma","parameter":"Cmax","detail":"","value":"496.6","variance":"± 117.5 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"free silybin B (SBb)","matrix":"plasma","parameter":"Cmax","detail":"","value":"406.8","variance":"± 59.2 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"free silybin A (SBa)","matrix":"plasma","parameter":"Cmax","detail":"","value":"723.0","variance":"± 163.8 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. Significance marker '*' vs silybin alone."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"free silybin B (SBb)","matrix":"plasma","parameter":"Cmax","detail":"","value":"658.4","variance":"± 73.3 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. Significance marker '***' vs silybin alone."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"total silybin A (SBa; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"25136","variance":"± 3279 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"total silybin B (SBb; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"52118","variance":"± 6413 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"total silybin A (SBa; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"91229","variance":"± 8992 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. Significance marker '***' vs silybin alone."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"total silybin B (SBb; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"139829","variance":"± 14912 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. Significance marker '***' vs silybin alone."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"total silybin A (SBa; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"27006","variance":"± 4267 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"total silybin B (SBb; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"54003","variance":"± 7131 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"total silybin A (SBa; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"94737","variance":"± 10557 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. Significance marker '***' vs silybin alone."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"total silybin B (SBb; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"141633","variance":"± 145967 (SD)","units":"ng h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. SD (145967) exceeds the mean as printed; verified on page image. Significance marker '***' vs silybin alone."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"total silybin A (SBa; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.40","variance":"± 0.42 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"total silybin B (SBb; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.00","variance":"± 0.93 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"total silybin A (SBa; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.92","variance":"± 0.20 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"total silybin B (SBb; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.92","variance":"± 0.20 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"total silybin A (SBa; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"6096","variance":"± 1642 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin (48% silybin A, 52% silybin B), in 35% PEG400:15% Cremophor EL:5% ethanol:45% saline (Sigma-Aldrich (silybin))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water ad libitum","n":"6","analyte":"total silybin B (SBb; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"10789","variance":"± 1170 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"total silybin A (SBa; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"21969","variance":"± 3243 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. Significance marker '***' vs silybin alone."},{"pmid":"28958806","species":"rodent","arm":"","form":"silybin + tangeretin in same solvent","forms":[],"dose":"50 (silybin) + 50 (tangeretin) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"total silybin B (SBb; free + glucuronide/sulfate conjugates after hydrolysis)","matrix":"plasma","parameter":"Cmax","detail":"","value":"34517","variance":"± 4622 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Methods state data are 'geometric mean ± S.D.' but Table 1 footnote says 'mean ± S.D. of 6 rats'. Significance marker '***' vs silybin alone."},{"pmid":"29026299","species":"rodent","arm":"","form":"silymarin powder (Sigma-Aldrich)","forms":["silymarin"],"dose":"20 mg/kg (silymarin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.672","variance":"± 0.141 (SD)","units":"µg/mL","location":"Table S1 (Supplementary material, p.7038)","quote":"","quoteCheck":"no quote","note":"Silymarin analyte measured by HPLC at 287 nm; n=6 per group stated in Methods"},{"pmid":"29026299","species":"rodent","arm":"","form":"silymarin powder (Sigma-Aldrich)","forms":["silymarin"],"dose":"20 mg/kg (silymarin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.441","variance":"± 0.315 (SD)","units":"h","location":"Table S1 (Supplementary material, p.7038)","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29026299","species":"rodent","arm":"","form":"silybon tablets","forms":[],"dose":"20 mg/kg (silymarin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.726","variance":"± 0.094 (SD)","units":"µg/mL","location":"Table S1 (Supplementary material, p.7038)","quote":"","quoteCheck":"no quote","note":"Silymarin analyte measured by HPLC at 287 nm; n=6 per group stated in Methods"},{"pmid":"29026299","species":"rodent","arm":"","form":"silybon tablets","forms":[],"dose":"20 mg/kg (silymarin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.215","variance":"± 0.217 (SD)","units":"h","location":"Table S1 (Supplementary material, p.7038)","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29026299","species":"rodent","arm":"","form":"SGNPs","forms":[],"dose":"20 mg/kg (silymarin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.037","variance":"± 0.116 (SD)","units":"µg/mL","location":"Table S1 (Supplementary material, p.7038)","quote":"","quoteCheck":"no quote","note":"Silymarin analyte measured by HPLC at 287 nm; n=6 per group stated in Methods"},{"pmid":"29026299","species":"rodent","arm":"","form":"SGNPs","forms":[],"dose":"20 mg/kg (silymarin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"3.246","variance":"± 0.148 (SD)","units":"h","location":"Table S1 (Supplementary material, p.7038)","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29026299","species":"rodent","arm":"","form":"GSGNPs","forms":[],"dose":"20 mg/kg (silymarin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.357","variance":"± 0.128 (SD)","units":"µg/mL","location":"Table S1 (Supplementary material, p.7038)","quote":"","quoteCheck":"no quote","note":"Silymarin analyte measured by HPLC at 287 nm; n=6 per group stated in Methods"},{"pmid":"29026299","species":"rodent","arm":"","form":"GSGNPs","forms":[],"dose":"20 mg/kg (silymarin equivalent)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"4.959","variance":"± 0.235 (SD)","units":"h","location":"Table S1 (Supplementary material, p.7038)","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin in N-octyl-O,N-carboxymethyl chitosan micelles","forms":["enhanced"],"dose":"9.1 mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"Cmax","detail":"","value":"2.35","variance":"± 0.54 (SD)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Plasma treated with β-glucuronidase so values are total (free + glucuronide-deconjugated) silybin per Methods; marker '*'"},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin in N-octyl-O,N-carboxymethyl chitosan micelles","forms":["enhanced"],"dose":"9.1 mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.52","variance":"± 0.17 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin in N-octyl-O,N-carboxymethyl chitosan micelles","forms":["enhanced"],"dose":"9.1 mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t (0-24 h per Methods; Table header 'AUC0−t h')","value":"8.47","variance":"± 2.06 (SD)","units":"μg h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"marker '**,†'"},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin suspension + verapamil","forms":[],"dose":"9.1 (SLB) + 25 (verapamil) mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.56","variance":"± 0.53 (SD)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Plasma treated with β-glucuronidase before HPLC per Methods"},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin suspension + verapamil","forms":[],"dose":"9.1 (SLB) + 25 (verapamil) mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.45","variance":"± 0.14 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin suspension + verapamil","forms":[],"dose":"9.1 (SLB) + 25 (verapamil) mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t (0-24 h per Methods; Table header 'AUC0−t h')","value":"4.44","variance":"± 0.81 (SD)","units":"μg h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"marker '*'"},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin suspension + OCC","forms":[],"dose":"9.1 (SLB) + 21.3 (OCC) mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.12","variance":"± 0.38 (SD)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Plasma treated with β-glucuronidase before HPLC per Methods"},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin suspension + OCC","forms":[],"dose":"9.1 (SLB) + 21.3 (OCC) mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.50","variance":"± 0.15 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin suspension + OCC","forms":[],"dose":"9.1 (SLB) + 21.3 (OCC) mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t (0-24 h per Methods; Table header 'AUC0−t h')","value":"3.40","variance":"± 0.64 (SD)","units":"μg h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin suspension","forms":[],"dose":"9.1 mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.98","variance":"± 0.32 (SD)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Plasma treated with β-glucuronidase before HPLC per Methods"},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin suspension","forms":[],"dose":"9.1 mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.28","variance":"± 0.15 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin suspension","forms":[],"dose":"9.1 mg/kg p.o.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t (0-24 h per Methods; Table header 'AUC0−t h')","value":"2.51","variance":"± 0.56 (SD)","units":"μg h/mL","location":"Table 2","quote":"AUC0−24 h of 2.51 ± 0.56 μg h mL−1","quoteCheck":"supported","note":""},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin solution","forms":[],"dose":"5 mg/kg i.v.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"Cmax","detail":"","value":"23.13","variance":"± 5.66 (SD)","units":"μg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Plasma treated with β-glucuronidase before HPLC per Methods"},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin solution","forms":[],"dose":"5 mg/kg i.v.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.083","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"i.v. group Tmax printed as 0.083 (first sampling time)"},{"pmid":"29162374","species":"rodent","arm":"","form":"silybin solution","forms":[],"dose":"5 mg/kg i.v.","doseBasis":"active compound","fed":"fasted overnight","n":"5","analyte":"silybin (after beta-glucuronidase treatment of plasma)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"15.49","variance":"± 2.31 (SD)","units":"μg h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30176941","species":"rodent","arm":"","form":"CS-LPN (PLGA, soybean lecithin, DSPE-PEG2000, chitosan)","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6 (Methods) / 5 (Fig. 5)","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"CS-LPNs vs silymarin suspension","value":"14.38","variance":"","units":"fold","location":"Abstract; Results (Pharmacokinetic study)","quote":"relative bioavailability of CS-LPNs was 1.23-fold and 14.38-fold higher than that of S-LPNs and silymarin suspension","quoteCheck":"supported","note":"Fold values; AUC basis/interval not stated in text; Abstract says 'oral bioavailability ... 14.38-fold higher than that from suspensions'"},{"pmid":"30176941","species":"rodent","arm":"","form":"CS-LPN (PLGA, soybean lecithin, DSPE-PEG2000, chitosan)","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6 (Methods) / 5 (Fig. 5)","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"CS-LPNs vs S-LPNs","value":"1.23","variance":"","units":"fold","location":"Results (Pharmacokinetic study); Discussion","quote":"the bioavailability of CS-LPNs was only 1.23-fold higher than that of the chitosan-free LPNs","quoteCheck":"supported","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin A (SBA)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-t) free","value":"1292","variance":"± 342 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Text gives 1292 ± 341 to 3534 ± 344 ng*h/ml"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin A (SBA)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-t) free","value":"3534","variance":"± 344 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Text gives 1292 ± 341 to 3534 ± 344 ng*h/ml"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin A (SBA)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-∞) free","value":"2305","variance":"± 1147 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin A (SBA)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-∞) free","value":"3599","variance":"± 410 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin A (SBA)","matrix":"plasma","parameter":"Tmax","detail":"free silybin","value":"1.50","variance":"± 0 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Tmax shown as mean ± SD; paper text: no significant difference in Tmax among groups"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin A (SBA)","matrix":"plasma","parameter":"Tmax","detail":"free silybin","value":"1.5","variance":"± 0 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Tmax shown as mean ± SD; paper text: no significant difference in Tmax among groups"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin A (SBA)","matrix":"plasma","parameter":"Cmax","detail":"free silybin","value":"507.7","variance":"± 115 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Text (Results p.10) gives 508 ± 114 to 1526 ± 126 ng/ml"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin A (SBA)","matrix":"plasma","parameter":"Cmax","detail":"free silybin","value":"1526","variance":"± 126 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Text (Results p.10) gives 508 ± 114 to 1526 ± 126 ng/ml"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin B (SBB)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-t) free","value":"1195","variance":"± 302 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Text gives 1195 ± 302 to 1808 ± 225 ng*h/ml"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin B (SBB)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-t) free","value":"1808","variance":"± 226 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Text gives 1195 ± 302 to 1808 ± 225 ng*h/ml"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin B (SBB)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-∞) free","value":"2087","variance":"± 932 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin B (SBB)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-∞) free","value":"1812","variance":"± 223 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin B (SBB)","matrix":"plasma","parameter":"Tmax","detail":"free silybin","value":"1.50","variance":"± 0 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Tmax shown as mean ± SD; paper text: no significant difference in Tmax among groups"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin B (SBB)","matrix":"plasma","parameter":"Tmax","detail":"free silybin","value":"1.29","variance":"± 0.51 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Tmax shown as mean ± SD; paper text: no significant difference in Tmax among groups"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin B (SBB)","matrix":"plasma","parameter":"Cmax","detail":"free silybin","value":"412.7","variance":"± 69.3 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Text (Results p.10) gives 413 ± 69 to 915 ± 150 ng/ml"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"free silybin B (SBB)","matrix":"plasma","parameter":"Cmax","detail":"free silybin","value":"915.2","variance":"± 151 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Text (Results p.10) gives 413 ± 69 to 915 ± 150 ng/ml"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin A (SBA)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-t) total (free + glucuronide/sulfate conjugates)","value":"12450","variance":"± 2553 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin A (SBA)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-t) total (free + glucuronide/sulfate conjugates)","value":"25921","variance":"± 2277 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin A (SBA)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-∞) total (free + glucuronide/sulfate conjugates)","value":"14475","variance":"± 4645 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin A (SBA)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-∞) total (free + glucuronide/sulfate conjugates)","value":"26906","variance":"± 3129 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin A (SBA)","matrix":"plasma","parameter":"Tmax","detail":"total silybin","value":"1.3","variance":"± 0.3 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Tmax shown as mean ± SD; paper text: no significant difference in Tmax among groups"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin A (SBA)","matrix":"plasma","parameter":"Tmax","detail":"total silybin","value":"1.8","variance":"± 0.3 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Tmax shown as mean ± SD; paper text: no significant difference in Tmax among groups"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin A (SBA)","matrix":"plasma","parameter":"Cmax","detail":"total silybin","value":"6427","variance":"± 2284 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin A (SBA)","matrix":"plasma","parameter":"Cmax","detail":"total silybin","value":"18194","variance":"± 3634 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin B (SBB)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-t) total (free + glucuronide/sulfate conjugates)","value":"53184","variance":"± 7340 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin B (SBB)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-t) total (free + glucuronide/sulfate conjugates)","value":"97584","variance":"± 23856 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin B (SBB)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-∞) total (free + glucuronide/sulfate conjugates)","value":"54680","variance":"± 7924 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin B (SBB)","matrix":"plasma","parameter":"AUC","detail":"AUC(0-∞) total (free + glucuronide/sulfate conjugates)","value":"98637","variance":"± 24179 (SD)","units":"ng · h/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin B (SBB)","matrix":"plasma","parameter":"Tmax","detail":"total silybin","value":"1.6","variance":"± 0.4 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Tmax shown as mean ± SD; paper text: no significant difference in Tmax among groups"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin B (SBB)","matrix":"plasma","parameter":"Tmax","detail":"total silybin","value":"1.8","variance":"± 0.3 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Tmax shown as mean ± SD; paper text: no significant difference in Tmax among groups"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin (oral; vehicle NR in PK section) (Sigma-Aldrich (reagent))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin B (SBB)","matrix":"plasma","parameter":"Cmax","detail":"total silybin","value":"9668","variance":"± 2134 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin B (SBB)","matrix":"plasma","parameter":"Cmax","detail":"total silybin","value":"23522","variance":"± 3643 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin A","matrix":"plasma","parameter":"Cmax","detail":"Cmax increase with baicalein (%)","value":"283%","variance":"","units":"%","location":"Results p.10","quote":"increase in Cmax of total silybin A and B by 283% and 243%, respectively","quoteCheck":"supported","note":"Printed as 'increase ... by 283%' (not a ratio); n not restated"},{"pmid":"30416442","species":"rodent","arm":"","form":"silybin with baicalein","forms":[],"dose":"50 (silybin) + 50 (baicalein) mg/kg each","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"total silybin B","matrix":"plasma","parameter":"Cmax","detail":"Cmax increase with baicalein (%)","value":"243%","variance":"","units":"%","location":"Results p.10","quote":"increase in Cmax of total silybin A and B by 283% and 243%, respectively","quoteCheck":"supported","note":"Printed as 'increase ... by 283%' (not a ratio); n not restated"},{"pmid":"30668388","species":"rodent","arm":"","form":"silybin (Sigma-Aldrich (silybin reagent; 48% SA, 52% SB))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"8","analyte":"free silybin A (SBa)","matrix":"plasma","parameter":"Cmax","detail":"free","value":"176","variance":"± 34 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 header says 'Mean pharmacokinetic parameters'; Methods says all data presented as geometric mean ± SD"},{"pmid":"30668388","species":"rodent","arm":"","form":"silybin + piperine (Sigma-Aldrich (silybin reagent; 48% SA, 52% SB))","forms":[],"dose":"50 (silybin) + 10 (piperine per Methods and Fig. 2 caption; 50 per Table 1 caption) mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"8","analyte":"free silybin A (SBa)","matrix":"plasma","parameter":"Cmax","detail":"free","value":"310","variance":"± 127 (SD)","units":"ng/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 header says 'Mean pharmacokinetic parameters'; Methods says all data presented as geometric mean ± SD"},{"pmid":"30668388","species":"rodent","arm":"","form":"silybin (Sigma-Aldrich (silybin reagent; 48% SA, 52% SB))","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"8","analyte":"free silybin A (SBa)","matrix":"plasma","parameter":"Tmax","detail":"free","value":"0.33","variance":"± 0.13 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 header says 'Mean pharmacokinetic parameters'; 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Results 3.5","quote":"The AUC0-1 values ... 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Protandim","doseBasis":"salt/compound","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"50.2","variance":"± 13.4 (NR)","units":"ng/mL","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 does not state what the ± represents"},{"pmid":"30904740","species":"rodent","arm":"","form":"Protandim (Protandim (LifeVantage))","forms":[],"dose":"364.5 mg/kg Protandim","doseBasis":"salt/compound","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"55.6","variance":"± 24.8 (NR)","units":"ng/mL","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 does not state what the ± represents"},{"pmid":"30904740","species":"rodent","arm":"","form":"Protandim (multi-herbal supplement containing milk thistle, ashwagandha, bacopa, turmeric, green tea extracts) (Protandim (LifeVantage))","forms":["silymarin"],"dose":"364.5 mg/kg Protandim","doseBasis":"salt/compound","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.0","variance":"","units":"h","location":"Table 5","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30904740","species":"rodent","arm":"","form":"Protandim (Protandim (LifeVantage))","forms":[],"dose":"364.5 mg/kg Protandim","doseBasis":"salt/compound","fed":"NR","n":"5","analyte":"silibinin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.1","variance":"","units":"h","location":"Table 5","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"35.6","variance":"± 16.2 (SD)","units":"µg·min/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"23.2","variance":"± 13.6 (SD)","units":"µg·min/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.250","variance":"± 0.056 (SD)","units":"µg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"30","variance":"± 2–30 (range)","units":"min","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Median (range) per Methods 3.8; variance = range"},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"26.9","variance":"± 11.2 (SD)","units":"µg·min/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"17.6","variance":"± 11.0 (SD)","units":"µg·min/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.455","variance":"± 0.277 (SD)","units":"µg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"10","variance":"± 5–30 (range)","units":"min","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Median (range) per Methods 3.8; variance = range"},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"50.6","variance":"± 24.9 (SD)","units":"µg·min/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"33.2","variance":"± 18.6 (SD)","units":"µg·min/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.744","variance":"± 0.331 (SD)","units":"µg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"10","variance":"± 5–20 (range)","units":"min","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Median (range) per Methods 3.8; variance = range"},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUCinf","value":"224.5","variance":"± 37.4 (SD)","units":"µg·min/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":"* Significantly different from the other groups (p < 0.05)"},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUClast","value":"207.0","variance":"± 28.0 (SD)","units":"µg·min/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":"* Significantly different from the other groups (p < 0.05)"},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"3.13","variance":"± 0.49 (SD)","units":"µg/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":"* Significantly different from the other groups (p < 0.05)"},{"pmid":"31185663","species":"rodent","arm":"","form":"Commercial silymarin soft gelatin capsule contents (undiluted liquid), manufacturer not disclosed (NR (names of manufacturers not disclosed))","forms":["silymarin"],"dose":"200 mg/kg as silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"20","variance":"± 10–20 (range)","units":"min","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Median (range) per Methods 3.8; variance = range"},{"pmid":"31207432","species":"rodent","arm":"","form":"silymarin in 0.25% CMC suspension","forms":["silymarin"],"dose":"200 mg/kg (equivalent of silybin)","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"100.45","variance":"± 3.45 (SEM)","units":"ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31207432","species":"rodent","arm":"","form":"silymarin in 0.25% CMC suspension","forms":["silymarin"],"dose":"200 mg/kg (equivalent of silybin)","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.50","variance":"± 0.0 (SEM)","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31207432","species":"rodent","arm":"","form":"silymarin in 0.25% CMC suspension","forms":["silymarin"],"dose":"200 mg/kg (equivalent of silybin)","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-2","value":"104.64","variance":"± 3.39 (SEM)","units":"h*ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31207432","species":"rodent","arm":"","form":"silymarin in 0.25% CMC suspension","forms":["silymarin"],"dose":"200 mg/kg (equivalent of silybin)","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"154.51","variance":"± 7.86 (SEM)","units":"h*ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31207432","species":"rodent","arm":"","form":"conventional liposomes (SPC:cholesterol 6:1:0) in distilled water","forms":["phytosome","enhanced"],"dose":"200 mg/kg (equivalent of silybin)","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"604.48","variance":"± 14.53 (SEM)","units":"ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31207432","species":"rodent","arm":"","form":"conventional liposomes (SPC:cholesterol 6:1:0) in distilled water","forms":["phytosome","enhanced"],"dose":"200 mg/kg (equivalent of silybin)","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.50","variance":"± 0 (SEM)","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31207432","species":"rodent","arm":"","form":"conventional liposomes (SPC:cholesterol 6:1:0) in distilled water","forms":["phytosome","enhanced"],"dose":"200 mg/kg (equivalent of silybin)","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-2","value":"430.64","variance":"± 8.52 (SEM)","units":"h*ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31207432","species":"rodent","arm":"","form":"conventional liposomes (SPC:cholesterol 6:1:0) in distilled water","forms":["phytosome","enhanced"],"dose":"200 mg/kg (equivalent of silybin)","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"464.37","variance":"± 9.3 (SEM)","units":"h*ng/ml","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31207432","species":"rodent","arm":"","form":"silymarin in 0.25% CMC suspension","forms":["silymarin"],"dose":"200 mg/kg (equivalent of silybin)","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"text","value":"100.45","variance":"± 3.45 (SEM)","units":"ng/ml","location":"Results, Bioavailability study p.8","quote":"Cmax ... was 100.45 ± 3.45 ng/ml for silymarin, with a tmax of 0.5 h","quoteCheck":"supported","note":"text value; same as Table 4"},{"pmid":"31207432","species":"rodent","arm":"","form":"conventional liposomes (SPC:cholesterol 6:1:0) in distilled water","forms":["phytosome","enhanced"],"dose":"200 mg/kg (equivalent of silybin)","doseBasis":"active compound","fed":"fasted 8 h","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"text","value":"604.48","variance":"± 14.53 (SEM)","units":"ng/ml","location":"Results, Bioavailability study p.8","quote":"","quoteCheck":"no quote","note":"text value; same as Table 4"},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"18.1","variance":"± 1.9 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"27.7","variance":"± 2.8 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"* P<=0.05 vs. control (unpaired t test)"},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"33.6","variance":"± 2.3 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"50.2","variance":"± 5.7 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"* P<=0.05 vs. control (unpaired t test)"},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"105.6","variance":"± 3.7 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"silychristin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"112.4","variance":"± 4.2 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"11.2","variance":"± 0.6 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"silydianin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"14.8","variance":"± 1.8 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"9.6","variance":"± 0.8 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"isosilybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"19.4","variance":"± 1.9 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"* P<=0.05 vs. control (unpaired t test)"},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"9.9","variance":"± 0.9 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"20.1","variance":"± 1.8 (SEM)","units":"nmol × min/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"* P<=0.05 vs. control (unpaired t test)"},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"total flavonolignans plus glucuronides","matrix":"plasma","parameter":"AUC","detail":"AUC0-120 min, total (flavonolignans plus glucuronides)","value":"353","variance":"± 32 (SEM)","units":"nmol × min/ml","location":"Results p.388 (text)","quote":"594 ± 71 vs. 353 ± 32 nmol × min/ml, mean ± S.E.M.","quoteCheck":"supported","note":"NASH 594 vs control 353"},{"pmid":"31420525","species":"rodent","arm":"","form":"silymarin (Sigma S0292) in saline with 15% ethanol and 30% PEG400 (Sigma Aldrich)","forms":["silymarin"],"dose":"10 mg/kg","doseBasis":"salt/compound","fed":"NR","n":"4","analyte":"total flavonolignans plus glucuronides","matrix":"plasma","parameter":"AUC","detail":"AUC0-120 min, total (flavonolignans plus glucuronides)","value":"594","variance":"± 71 (SEM)","units":"nmol × min/ml","location":"Results p.388 (text)","quote":"594 ± 71 vs. 353 ± 32 nmol × min/ml, mean ± S.E.M.","quoteCheck":"supported","note":"1.7-fold vs control as printed"},{"pmid":"31923602","species":"rodent","arm":"","form":"silybin-phospholipid complex nanosuspension (SPCs-NPs) in 0.5% CMC","forms":["enhanced"],"dose":"50 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"Tmax","value":"1.50","variance":"± 0.13 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31923602","species":"rodent","arm":"","form":"silybin-phospholipid complex nanosuspension (SPCs-NPs) in 0.5% CMC","forms":["enhanced"],"dose":"50 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"9407.03","variance":"± 87.45 (SD)","units":"ng/ml × h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31923602","species":"rodent","arm":"","form":"SPCs + excipients physical mixture in 0.5% CMC","forms":[],"dose":"50 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"Tmax","value":"2.00","variance":"± 0.21 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31923602","species":"rodent","arm":"","form":"SPCs + excipients physical mixture in 0.5% CMC","forms":[],"dose":"50 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"5395.86","variance":"± 67.32 (SD)","units":"ng/ml × h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"31923602","species":"rodent","arm":"","form":"silybin physical mixture in 0.5% CMC","forms":[],"dose":"50 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"Tmax","value":"0.17","variance":"± 0.023 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"*** p<0.001 vs SPCs-NPs and SPCs physical mixture"},{"pmid":"31923602","species":"rodent","arm":"","form":"silybin physical mixture in 0.5% CMC","forms":[],"dose":"50 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"75.44","variance":"± 8.19 (SD)","units":"ng/ml × h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"*** p<0.001 vs SPCs-NPs and SPCs physical mixture"},{"pmid":"31923602","species":"rodent","arm":"","form":"silybin physical mixture in 0.5% CMC","forms":[],"dose":"50 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞ (text)","value":"75.44","variance":"± 8.19 (SD)","units":"ng/ml × h","location":"Results 3.9 p.9","quote":"whose AUC0-∞ was only 75.44 ± 8.19 ng/ml × h","quoteCheck":"supported","note":"text, same as Table 1"},{"pmid":"31923602","species":"rodent","arm":"","form":"silybin-phospholipid complex nanosuspension (SPCs-NPs) in 0.5% CMC","forms":["enhanced"],"dose":"50 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞ (text)","value":"9407.03","variance":"± 87.45 (SD)","units":"ng/ml × h","location":"Results 3.9 p.9","quote":"The AUC0-∞ of SPCs-NPs group was (9407.03 ± 87.45) ng/ml × h","quoteCheck":"supported","note":"text, same as Table 1"},{"pmid":"32337654","species":"rodent","arm":"","form":"pure silybin in 0.5% CMC","forms":[],"dose":"70 mg/kg (as SLY equivalent)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"3.52","variance":"± 0.88 (NR)","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"variance type not stated (± as printed)."},{"pmid":"32337654","species":"rodent","arm":"","form":"SLY/MOG-V solid dispersion particles (1:20) in 0.5% CMC","forms":["enhanced"],"dose":"70 mg/kg (as SLY equivalent)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"568.45","variance":"± 250.20 (NR)","units":"ng/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"variance type not stated (± as printed)."},{"pmid":"32337654","species":"rodent","arm":"","form":"pure silybin in 0.5% CMC","forms":[],"dose":"70 mg/kg (as SLY equivalent)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"1122","variance":"± 452 (NR)","units":"ng·min/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"variance type not stated (± as printed)."},{"pmid":"32337654","species":"rodent","arm":"","form":"SLY/MOG-V solid dispersion particles (1:20) in 0.5% CMC","forms":["enhanced"],"dose":"70 mg/kg (as SLY equivalent)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"27,481","variance":"± 13,142 (NR)","units":"ng·min/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"variance type not stated (± as printed)."},{"pmid":"32337654","species":"rodent","arm":"","form":"pure silybin in 0.5% CMC","forms":[],"dose":"70 mg/kg (as SLY equivalent)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"2401","variance":"± 1101 (NR)","units":"ng·min/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"variance type not stated (± as printed)."},{"pmid":"32337654","species":"rodent","arm":"","form":"SLY/MOG-V solid dispersion particles (1:20) in 0.5% CMC","forms":["enhanced"],"dose":"70 mg/kg (as SLY equivalent)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"32,100","variance":"± 12,472 (NR)","units":"ng·min/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":"variance type not stated (± as printed)."},{"pmid":"32337654","species":"rodent","arm":"","form":"pure silybin in 0.5% CMC","forms":[],"dose":"105 mg/kg (as SLY equivalent)","doseBasis":"active compound","fed":"NR","n":"3","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-2 h","value":"0.3","variance":"± 0.1 (NR)","units":"μg·min/g or mL","location":"Table III","quote":"","quoteCheck":"no quote","note":"units as printed 'μg·min/g or mL' (g for tissues, mL for plasma); variance type not stated"},{"pmid":"32337654","species":"rodent","arm":"","form":"SLY/MOG-V SDPs in 0.5% CMC","forms":[],"dose":"105 mg/kg (as SLY equivalent)","doseBasis":"active compound","fed":"NR","n":"3","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-2 h","value":"35.6","variance":"± 14.3 (NR)","units":"μg·min/g or mL","location":"Table III","quote":"","quoteCheck":"no quote","note":"units as printed 'μg·min/g or mL'; variance type not stated"},{"pmid":"32473632","species":"rodent","arm":"","form":"pHPMA-coated WGA-modified LPNs","forms":[],"dose":"80 mg/kg (equivalent doses of SLB and CT)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"silibinin (SLB)","matrix":"plasma","parameter":"AUC","detail":"AUC (interval not stated)","value":"9,796.75","variance":"± 846.76 (SD)","units":"μg/L∙h","location":"Results, Pharmacokinetics studies, p.8","quote":"The area under the curve (AUC) of the S/C-pW-LPNs for SLB was 9,796.75 ± 846.76 μg/L∙h.","quoteCheck":"supported","note":"AUC interval (0-t or 0-∞) NR; ± taken as SD per Statistical analysis section (mean ± SD)"},{"pmid":"32473632","species":"rodent","arm":"","form":"pHPMA-coated WGA-modified LPNs","forms":[],"dose":"80 mg/kg (equivalent doses of SLB and CT)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"silibinin (SLB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"pW-LPNs vs suspension","value":"15.5 ×","variance":"","units":"fold","location":"Results, Pharmacokinetics studies, p.8","quote":"The relative bioavailabilities of SLB and CT in the S/W-pW-LPNs were 15.5 × and 11.4 × higher than those in the suspensions","quoteCheck":"supported","note":"paper writes 'S/W-pW-LPNs' (likely S/C-pW-LPNs); text says 'the suspensions'"},{"pmid":"33246779","species":"rodent","arm":"","form":"unprocessed silybin powder in 0.5% CMC-Na (NR (silybin from NanJing QingYun Biotechnology))","forms":[],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"260.41","variance":"± 67.70 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: ##. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"unprocessed silybin powder in 0.5% CMC-Na (NR (silybin from NanJing QingYun Biotechnology))","forms":[],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"1.83","variance":"± 0.41 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: ##. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"unprocessed silybin powder in 0.5% CMC-Na (NR (silybin from NanJing QingYun Biotechnology))","forms":[],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC0-24h","value":"2091.91","variance":"± 191.91 (SD)","units":"ng hmL (as printed in Table 3; slash not visible)","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: ##. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"silybin nanocrystals (wet media milling, freeze-dried with mannitol)","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"548.82","variance":"± 26.80 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: **,##. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"silybin nanocrystals (wet media milling, freeze-dried with mannitol)","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"0.96","variance":"± 0.10 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: **,##. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"silybin nanocrystals (wet media milling, freeze-dried with mannitol)","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC0-24h","value":"3903.82","variance":"± 510.45 (SD)","units":"ng hmL (as printed in Table 3; slash not visible)","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: **,##. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"silybin nanocrystal-in-alginate/chitosan microspheres, uncoated","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"463.08","variance":"± 24.12 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: **,#. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"silybin nanocrystal-in-alginate/chitosan microspheres, uncoated","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"2.33","variance":"± 0.82 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: ##. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"silybin nanocrystal-in-alginate/chitosan microspheres, uncoated","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC0-24h","value":"4983.03","variance":"± 467.00 (SD)","units":"ng hmL (as printed in Table 3; slash not visible)","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: **,#. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"coated mucoadhesive silybin nanocrystal-in-microspheres","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"427.52","variance":"± 30.10 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: **. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"coated mucoadhesive silybin nanocrystal-in-microspheres","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"6.00","variance":"± 1.27 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: **. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"coated mucoadhesive silybin nanocrystal-in-microspheres","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC0-24h","value":"5885.02","variance":"± 623.43 (SD)","units":"ng hmL (as printed in Table 3; slash not visible)","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 flags: p-value symbols as printed: **. Dose basis inconsistent (35 vs 100 mg/kg)."},{"pmid":"33246779","species":"rodent","arm":"","form":"coated mucoadhesive silybin nanocrystal-in-microspheres","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC0-24h (text)","value":"5885.02","variance":"± 623.43 (SD)","units":"ng h mL (as printed in text)","location":"Results 3.4 para 2","quote":"a 3-fold increase of bioavailability (AUC0-24h = 5885.02 ± 623.43 ng h mL) was observed in the coated SBN–C/MS groups","quoteCheck":"supported","note":"same value as Table 3"},{"pmid":"33246779","species":"rodent","arm":"","form":"unprocessed silybin powder in 0.5% CMC-Na (NR (silybin from NanJing QingYun Biotechnology))","forms":[],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC0-24h (text)","value":"2091.91","variance":"± 191.91 (SD)","units":"ng h mL (as printed in text)","location":"Results 3.4 para 2","quote":"compared to the SB groups (AUC0-24h = 2091.91 ± 191.91 ng h mL)","quoteCheck":"supported","note":"same value as Table 3"},{"pmid":"33246779","species":"rodent","arm":"","form":"silybin nanocrystals (wet media milling, freeze-dried with mannitol)","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"Cmax","detail":"Cmax % higher than unprocessed SB","value":"110.75","variance":"","units":"%","location":"Results 3.4 para 2","quote":"The peak concentrations of SB-NCs, uncoated SB–NC/MS and coated SBNC/MS were 110.75 %, 77.83 % and 64.17 –% higher","quoteCheck":"supported","note":"percent difference as printed by authors"},{"pmid":"33246779","species":"rodent","arm":"","form":"silybin nanocrystal-in-alginate/chitosan microspheres, uncoated","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"Cmax","detail":"Cmax % higher than unprocessed SB","value":"77.83","variance":"","units":"%","location":"Results 3.4 para 2","quote":"110.75 %, 77.83 % and 64.17 –% higher than that of unprocessed SB","quoteCheck":"supported","note":"percent difference as printed by authors"},{"pmid":"33246779","species":"rodent","arm":"","form":"coated mucoadhesive silybin nanocrystal-in-microspheres","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"Cmax","detail":"Cmax % higher than unprocessed SB","value":"64.17","variance":"","units":"%","location":"Results 3.4 para 2","quote":"110.75 %, 77.83 % and 64.17 –% higher than that of unprocessed SB","quoteCheck":"supported","note":"percent difference as printed by authors; '–%' appears in text layer"},{"pmid":"33246779","species":"rodent","arm":"","form":"coated mucoadhesive silybin nanocrystal-in-microspheres","forms":["enhanced"],"dose":"35 (Methods 2.8.1) / 100 (Sect. 3.4, Fig. 5C caption) mg/kg","doseBasis":"active compound","fed":"fasted overnight, fed 3-4 h after dosing","n":"6","analyte":"silybin (SB)","matrix":"rat plasma","parameter":"relative_bioavailability","detail":"AUC0-24h ratio, coated SB-NC/MS vs unprocessed SB ('3-fold')","value":"3-fold","variance":"","units":"fold","location":"Abstract; Results 3.4","quote":"a significant 3-fold increase of drug oral bioavailability compared to unprocessed SB","quoteCheck":"supported","note":"Authors' wording; Eq. 8 defines relative bioavailability but no percentage value is printed. Not computed here."},{"pmid":"33257158","species":"rodent","arm":"","form":"free silibinin aqueous suspension","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"26.08","variance":"± 1.43 (NR)","units":"μg/L","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"free silibinin aqueous suspension","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"1","variance":"± 0.15 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"free silibinin aqueous suspension","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC(0-t)","value":"102.63","variance":"± 7.15 (NR)","units":"μg/L*h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"free silibinin aqueous suspension","forms":[],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC(0-∞)","value":"147.51","variance":"± 8.42 (NR)","units":"μg/L*h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles by liquid antisolvent precipitation, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"60.31","variance":"± 8.98 (NR)","units":"μg/L","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles by liquid antisolvent precipitation, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"0.17","variance":"± 0.05 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles by liquid antisolvent precipitation, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC(0-t)","value":"206.51","variance":"± 12.24 (NR)","units":"μg/L*h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles by liquid antisolvent precipitation, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC(0-∞)","value":"210.71","variance":"± 14.22 (NR)","units":"μg/L*h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles in porous starch, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"87.71","variance":"± 7.24 (NR)","units":"μg/L","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles in porous starch, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"1.5","variance":"± 0.1 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles in porous starch, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC(0-t)","value":"439.55","variance":"± 8.76 (NR)","units":"μg/L*h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles in porous starch, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC(0-∞)","value":"442.66","variance":"± 8.54 (NR)","units":"μg/L*h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Variance type not stated in paper (± as printed); n per group not stated"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles in porous starch, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"Cmax","detail":"fold vs free SLB","value":"3.36","variance":"","units":"fold","location":"Results 3.5","quote":"the Cmax and the AUC(0–t) values of the SNPS ... were 3.36 and 4.28-fold","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles in porous starch, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC(0-t) fold vs free SLB","value":"4.28","variance":"","units":"fold","location":"Results 3.5; Conclusion","quote":"were 3.36 and 4.28-fold","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles by liquid antisolvent precipitation, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"Cmax","detail":"fold vs free SLB","value":"2.31","variance":"","units":"fold","location":"Results 3.5","quote":"SN ... were 2.31 and 2.01-fold of the free SLB","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"33257158","species":"rodent","arm":"","form":"silibinin nanoparticles by liquid antisolvent precipitation, aqueous suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted overnight, free access to water","n":"NR","analyte":"silibinin (SLB)","matrix":"rat plasma","parameter":"AUC","detail":"AUC(0-t) fold vs free SLB","value":"2.01","variance":"","units":"fold","location":"Results 3.5","quote":"SN ... were 2.31 and 2.01-fold of the free SLB","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin (Sigma-Aldrich S0292) in vehicle (20% propylene glycol, 45% PEG400, 35% water) (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"7","analyte":"silybin A (SA)","matrix":"rat plasma","parameter":"AUC","detail":"AUC (partial: 0-27 h for glucuronides; 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tmax = median (min, max)."},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin (Sigma-Aldrich S0292) in vehicle (20% propylene glycol, 45% PEG400, 35% water) (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"7","analyte":"silybin A-4''-O-beta-D-glucuronide (S4G)","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"2.0","variance":"","units":"µmol/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 note: data are geometric means with 90% CI (AUC, CL/F, Cmax, t1/2); tmax = median (min, max). Printed Cmax point estimate 2.0 lies outside its printed CI (2.5, 3.6); recorded as printed (page image checked)."},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin (Sigma-Aldrich S0292) in vehicle (20% propylene glycol, 45% PEG400, 35% water) (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"7","analyte":"silybin A-4''-O-beta-D-glucuronide (S4G)","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"2.0","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 note: data are geometric means with 90% CI (AUC, CL/F, Cmax, t1/2); tmax = median (min, max)."},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin in vehicle (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin A-4''-O-beta-D-glucuronide (S4G)","matrix":"rat plasma","parameter":"AUC","detail":"AUC (partial: 0-27 h for glucuronides; 0-2 h for SC and TF; total AUC for SA, SB, IA, IB per Methods 2.7)","value":"160.3","variance":"","units":"h*µmol/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 note: data are geometric means with 90% CI (AUC, CL/F, Cmax, t1/2); tmax = median (min, max)."},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin in vehicle (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin A-4''-O-beta-D-glucuronide (S4G)","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"12.6","variance":"","units":"µmol/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 note: data are geometric means with 90% CI (AUC, CL/F, Cmax, t1/2); tmax = median (min, max)."},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin in vehicle (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 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(AUC, CL/F, Cmax, t1/2); tmax = median (min, max)."},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin (Sigma-Aldrich S0292) in vehicle (20% propylene glycol, 45% PEG400, 35% water) (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"7","analyte":"silybin A-7-O-beta-D-glucuronide (S7G)","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"3.0","variance":"","units":"µmol/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 note: data are geometric means with 90% CI (AUC, CL/F, Cmax, t1/2); tmax = median (min, max)."},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin (Sigma-Aldrich S0292) in vehicle (20% propylene glycol, 45% PEG400, 35% water) (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"7","analyte":"silybin A-7-O-beta-D-glucuronide (S7G)","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"2.0","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 note: data are geometric means with 90% CI (AUC, CL/F, Cmax, t1/2); tmax = median (min, max)."},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin in vehicle (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin A-7-O-beta-D-glucuronide (S7G)","matrix":"rat plasma","parameter":"AUC","detail":"AUC (partial: 0-27 h for glucuronides; 0-2 h for SC and TF; total AUC for SA, SB, IA, IB per Methods 2.7)","value":"154.3","variance":"","units":"h*µmol/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1 note: data are geometric means with 90% CI (AUC, CL/F, Cmax, t1/2); tmax = median (min, max)."},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin in vehicle (Sigma-Aldrich, lot 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silymarin)","forms":["silymarin"],"dose":"0 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"7","analyte":"pitavastatin","matrix":"rat plasma","parameter":"AUC","detail":"AUC0-27h","value":"3.1","variance":"","units":"h*µmol/L","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Bonferroni post-hoc flags as printed: none (a: p≤.05 vs respective vehicle; b: vs control vehicle; c: vs control silymarin)"},{"pmid":"33587330","species":"rodent","arm":"","form":"vehicle only (no silymarin)","forms":["silymarin"],"dose":"0 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"7","analyte":"pitavastatin","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"0.8","variance":"","units":"µmol/L","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Flags as printed: none"},{"pmid":"33587330","species":"rodent","arm":"","form":"vehicle only (no silymarin)","forms":["silymarin"],"dose":"0 mg/kg","doseBasis":"NR","fed":"fasted 12 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plasma","parameter":"AUC","detail":"AUC0-27h","value":"9.1","variance":"","units":"h*µmol/L","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Bonferroni post-hoc flags as printed: b,c (a: p≤.05 vs respective vehicle; b: vs control vehicle; c: vs control silymarin)"},{"pmid":"33587330","species":"rodent","arm":"","form":"vehicle only (no silymarin)","forms":["silymarin"],"dose":"0 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"pitavastatin","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"3.1","variance":"","units":"µmol/L","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Flags as printed: b"},{"pmid":"33587330","species":"rodent","arm":"","form":"vehicle only (no silymarin)","forms":["silymarin"],"dose":"0 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"pitavastatin","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"0.50","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no 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b,c"},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin in vehicle (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"pitavastatin","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"1.25","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Flags as printed: a,b"},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin in vehicle (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"pitavastatin","matrix":"rat plasma","parameter":"AUC","detail":"AUC0-27h fold vs control vehicle","value":"5.1-fold","variance":"","units":"fold","location":"Results 3.2","quote":"The combination of silymarin and NASH increased pitavastatin AUC0-27h 5.1-fold compared to the control vehicle group","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"33587330","species":"rodent","arm":"","form":"vehicle only (no silymarin)","forms":["silymarin"],"dose":"0 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"pitavastatin","matrix":"rat plasma","parameter":"AUC","detail":"AUC0-27h fold vs control vehicle (NASH alone)","value":"2.9-fold","variance":"","units":"fold","location":"Results 3.2","quote":"NASH alone increased pitavastatin AUC0-27h 2.9-fold (NASH vehicle compared to control vehicle)","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin (Sigma-Aldrich S0292) in vehicle (20% propylene glycol, 45% PEG400, 35% water) (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"7","analyte":"pitavastatin","matrix":"rat plasma","parameter":"AUC","detail":"AUC0-27h fold vs respective vehicle","value":"1.8-fold","variance":"","units":"fold","location":"Results 3.2","quote":"Silymarin increased pitavastatin AUC0-27h 1.8-fold in both the control silymarin and NASH silymarin groups","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin in vehicle (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"pitavastatin","matrix":"rat plasma","parameter":"AUC","detail":"AUC0-27h fold vs respective vehicle","value":"1.8-fold","variance":"","units":"fold","location":"Results 3.2","quote":"Silymarin increased pitavastatin AUC0-27h 1.8-fold in both the control silymarin and NASH silymarin groups","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"33587330","species":"rodent","arm":"","form":"vehicle only (no silymarin)","forms":["silymarin"],"dose":"0 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"pitavastatin","matrix":"rat plasma","parameter":"Cmax","detail":"Cmax fold vs control (no silymarin)","value":"3.9-fold","variance":"","units":"fold","location":"Results 3.2","quote":"NASH increased pitavastatin Cmax by 3.9-fold in the absence of silymarin","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"33587330","species":"rodent","arm":"","form":"silymarin in vehicle (Sigma-Aldrich, lot BCBT9170)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"pitavastatin","matrix":"rat plasma","parameter":"Cmax","detail":"Cmax fold vs control (with silymarin)","value":"2.8-fold","variance":"","units":"fold","location":"Results 3.2","quote":"and 2.8-fold in the presence of silymarin","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"33616078","species":"rodent","arm":"","form":"silymarin encapsulated in siRNP (about 110 nm after loading)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silymarin","matrix":"mouse plasma","parameter":"Tmax","detail":"time window of plasma detection","value":"0.5 to 2 h","variance":"","units":"h","location":"Results 3 (p. 520)","quote":"absorption of silymarin was detected in the plasma within 0.5 to 2 h after oral administration of SM@siRNP","quoteCheck":"supported","note":"stated as detection window, not a Tmax value"},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin suspended in 0.5% CMC","forms":["silymarin"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"106","variance":"± 14.9 (SD)","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: none. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin suspended in 0.5% CMC","forms":["silymarin"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"0.56","variance":"± 0.31 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: none. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin suspended in 0.5% CMC","forms":["silymarin"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"AUC","detail":"AUC24h (zero to 24 h)","value":"578","variance":"± 225 (SD)","units":"ng·h/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: none. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin suspended in 0.5% CMC","forms":["silymarin"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"AUC","detail":"AUC∞ (zero to infinity)","value":"634","variance":"± 239 (SD)","units":"n·h/mL (as printed in Table 1; 'n' appears to be a typo for ng)","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: none. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"427","variance":"± 147 (SD)","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: *. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"0.40","variance":"± 0.14 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: none. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"AUC","detail":"AUC24h (zero to 24 h)","value":"957","variance":"± 350 (SD)","units":"ng·h/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: *. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"AUC","detail":"AUC∞ (zero to infinity)","value":"1060","variance":"± 406 (SD)","units":"n·h/mL (as printed in Table 1; 'n' appears to be a typo for ng)","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: *. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin suspended in 0.5% CMC","forms":["silymarin"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"146","variance":"± 48.1 (SD)","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: none. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin suspended in 0.5% CMC","forms":["silymarin"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"0.45","variance":"± 0.11 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: none. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin suspended in 0.5% CMC","forms":["silymarin"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"AUC","detail":"AUC24h (zero to 24 h)","value":"547","variance":"± 131 (SD)","units":"ng·h/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: none. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin suspended in 0.5% CMC","forms":["silymarin"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"AUC","detail":"AUC∞ (zero to infinity)","value":"587","variance":"± 138 (SD)","units":"n·h/mL (as printed in Table 1; 'n' appears to be a typo for ng)","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: none. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"412","variance":"± 168 (SD)","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: *. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"Tmax","detail":"","value":"0.44","variance":"± 0.13 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: none. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"AUC","detail":"AUC24h (zero to 24 h)","value":"2040","variance":"± 435 (SD)","units":"ng·h/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: *,+. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"AUC","detail":"AUC∞ (zero to infinity)","value":"2190","variance":"± 374 (SD)","units":"n·h/mL (as printed in Table 1; 'n' appears to be a typo for ng)","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1: * p<0.05 vs silymarin itself; + p<0.05 vs single administration. Flag printed: *,+. Mean ± SD (Methods 2.9); n = 4 per group (Fig. 5 legend)."},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"Cmax","detail":"fold vs silymarin single","value":"4.0-fold","variance":"","units":"fold","location":"Results 3.4","quote":"the maximum plasma concentration (Cmax) and the area under the plasma concentration curve (AUC) ... were 4.0- and 1.6-fold, respectively, greater","quoteCheck":"value not in quote","note":"fold-change as printed by authors"},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"AUC","detail":"fold vs silymarin single","value":"1.6-fold","variance":"","units":"fold","location":"Results 3.4; Discussion","quote":"were 4.0- and 1.6-fold, respectively, greater than those for silymarin only","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"AUC","detail":"fold vs silymarin repeated","value":"3.7-fold","variance":"","units":"fold","location":"Results 3.4; Discussion","quote":"the fold increase in the silybin AUC was greater (3.7-fold) in the repeated administration of the silymarin-SD group than silymarin itself (1.6-fold)","quoteCheck":"supported","note":"fold-change as printed by authors; sentence wording confusing, '1.6-fold' refers to single-dose comparison"},{"pmid":"33925040","species":"rodent","arm":"","form":"silymarin-TPGS solid dispersion suspended in 0.5% CMC","forms":["enhanced"],"dose":"20 (as silybin) mg/kg","doseBasis":"active compound","fed":"NR for PK dosing (rats were fasted 16 h before the intestinal-permeability tissue collection per Methods 2.5)","n":"4","analyte":"silybin","matrix":"rat plasma","parameter":"AUC","detail":"fold vs silymarin-SD single administration","value":"2.1-fold","variance":"","units":"fold","location":"Discussion","quote":"plasma AUC was increased 2.1-fold when compared to the single administration of silymarin-SD","quoteCheck":"supported","note":"fold-change as printed by authors"},{"pmid":"35560136","species":"rodent","arm":"","form":"Silibinin-Sol (pure SB) (Sigma Aldrich (SB))","forms":[],"dose":"1.8 (PK methods p.10) / 2.0 (p.10 and p.22 text, IV tail vein) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"20.15","variance":"± 2.32 (SD)","units":"μg/mL","location":"Table 5","quote":"","quoteCheck":"no quote","note":""},{"pmid":"35560136","species":"rodent","arm":"","form":"Silibinin-Sol (pure SB) (Sigma Aldrich (SB))","forms":[],"dose":"1.8 (PK methods p.10) / 2.0 (p.10 and p.22 text, IV tail vein) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"Tmax","detail":"","value":"4.1","variance":"± 2.02 (SD)","units":"NR","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Tmax unit not printed in Table 5; text p.24 also gives no unit"},{"pmid":"35560136","species":"rodent","arm":"","form":"Silibinin-Sol (pure SB) (Sigma Aldrich (SB))","forms":[],"dose":"1.8 (PK methods p.10) / 2.0 (p.10 and p.22 text, IV tail vein) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUCtotal","value":"225.54","variance":"± 10.21 (SD)","units":"μg h/mL","location":"Table 5","quote":"","quoteCheck":"no quote","note":""},{"pmid":"35560136","species":"rodent","arm":"","form":"SB-loaded PCL/Pluronic F68 nanoparticles","forms":["enhanced"],"dose":"1.8 (dose equivalent of SB) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"54.10","variance":"± 1.02 (SD)","units":"μg/mL","location":"Table 5","quote":"","quoteCheck":"no quote","note":""},{"pmid":"35560136","species":"rodent","arm":"","form":"SB-loaded PCL/Pluronic F68 nanoparticles","forms":["enhanced"],"dose":"1.8 (dose equivalent of SB) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"Tmax","detail":"","value":"4.3","variance":"± 1.54 (SD)","units":"NR","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Tmax unit not printed in Table 5; text p.24 also gives no unit"},{"pmid":"35560136","species":"rodent","arm":"","form":"SB-loaded PCL/Pluronic F68 nanoparticles","forms":["enhanced"],"dose":"1.8 (dose equivalent of SB) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUCtotal","value":"325.21","variance":"± 9.23 (SD)","units":"μg h/mL","location":"Table 5","quote":"","quoteCheck":"no quote","note":""},{"pmid":"35560136","species":"rodent","arm":"","form":"SB-loaded PCL/Pluronic F68 nanoparticles (lyophilized, with lactose 1:1)","forms":["enhanced"],"dose":"1.8 (dose equivalent of SB) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"","value":"80.11","variance":"± 2.14 (SD)","units":"μg/mL","location":"Table 5","quote":"","quoteCheck":"no quote","note":""},{"pmid":"35560136","species":"rodent","arm":"","form":"SB-loaded PCL/Pluronic F68 nanoparticles (lyophilized, with lactose 1:1)","forms":["enhanced"],"dose":"1.8 (dose equivalent of SB) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"Tmax","detail":"","value":"6.2","variance":"± 2.85 (SD)","units":"NR","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Tmax unit not printed in Table 5; text p.24 also gives no unit"},{"pmid":"35560136","species":"rodent","arm":"","form":"SB-loaded PCL/Pluronic F68 nanoparticles (lyophilized, with lactose 1:1)","forms":["enhanced"],"dose":"1.8 (dose equivalent of SB) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUCtotal","value":"587.31","variance":"± 14.12 (SD)","units":"μg h/mL","location":"Table 5","quote":"","quoteCheck":"no quote","note":""},{"pmid":"35560136","species":"rodent","arm":"","form":"Silibinin-Sol (pure SB) (Sigma Aldrich (SB))","forms":[],"dose":"1.8 (PK methods p.10) / 2.0 (p.10 and p.22 text, IV tail vein) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel as printed in Table 5 (row 'Frel')","value":"1","variance":"","units":"NR","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 Frel column for arm A = 1 (apparent reference). Text p.25 defines Frel as AUCtotal(inhaled NP)/AUCtotal(IV NP) and reports 4.20; Table 5 shows IV NP = 1.89 and silibinin solution = 1, so reference is inconsistent between table and text."},{"pmid":"35560136","species":"rodent","arm":"","form":"SB-loaded PCL/Pluronic F68 nanoparticles","forms":["enhanced"],"dose":"1.8 (dose equivalent of SB) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel as printed in Table 5 (row 'Frel')","value":"1.89","variance":"","units":"NR","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 Frel column for arm A = 1 (apparent reference). Text p.25 defines Frel as AUCtotal(inhaled NP)/AUCtotal(IV NP) and reports 4.20; Table 5 shows IV NP = 1.89 and silibinin solution = 1, so reference is inconsistent between table and text."},{"pmid":"35560136","species":"rodent","arm":"","form":"SB-loaded PCL/Pluronic F68 nanoparticles (lyophilized, with lactose 1:1)","forms":["enhanced"],"dose":"1.8 (dose equivalent of SB) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel as printed in Table 5 (row 'Frel')","value":"4.20","variance":"","units":"NR","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 Frel column for arm A = 1 (apparent reference). Text p.25 defines Frel as AUCtotal(inhaled NP)/AUCtotal(IV NP) and reports 4.20; Table 5 shows IV NP = 1.89 and silibinin solution = 1, so reference is inconsistent between table and text."},{"pmid":"35560136","species":"rodent","arm":"","form":"SB-loaded PCL/Pluronic F68 nanoparticles (lyophilized, with lactose 1:1)","forms":["enhanced"],"dose":"1.8 (dose equivalent of SB) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel inhaled NP vs IV NP (text)","value":"4.20","variance":"","units":"fold","location":"Results p.25, Pharmacokinetic study","quote":"prepared Inhalable nanoparticles exhibited 4.20 folds more bioavailable than the Nanoparticles by IV Route","quoteCheck":"supported","note":"Text says 4.20; Table 5 AUC ratio not stated by authors"},{"pmid":"35560136","species":"rodent","arm":"","form":"SB-loaded PCL/Pluronic F68 nanoparticles (lyophilized, with lactose 1:1)","forms":["enhanced"],"dose":"1.8 (dose equivalent of SB) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"inhaled NP vs IV NP (text)","value":"nearly four times higher","variance":"","units":"NR","location":"Results p.24","quote":"Cmax achieved with inhalable nanoparticles was nearly four times higher","quoteCheck":"supported","note":"Qualitative statement; Table 5 Cmax values are 80.11 vs 54.10"},{"pmid":"35708053","species":"rodent","arm":"","form":"Sofosbuvir + ledipasvir","forms":[],"dose":"40 SFB and 9 LED mg/kg","doseBasis":"NR","fed":"fasted ~12 h","n":"4","analyte":"sofosbuvir","matrix":"plasma","parameter":"AUC","detail":"AUC (model-fitted)","value":"2,185","variance":"± 128.2 (SEM)","units":"ng/ml h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table 4 footnote: AUC mean ± SEM; K and t1/2 mean and 95% CI"},{"pmid":"35708053","species":"rodent","arm":"","form":"Silymarin (SLY) with SFB and LED (NR (SLY 88% provided by Arab Company for Gelatin and Pharmaceutical Products))","forms":["silymarin"],"dose":"40 SFB, 9 LED, 30 SLY mg/kg","doseBasis":"NR","fed":"fasted ~12 h","n":"4","analyte":"sofosbuvir","matrix":"plasma","parameter":"AUC","detail":"AUC (model-fitted)","value":"2,811","variance":"± 103.9 (SEM)","units":"ng/ml h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table 4 footnote: AUC mean ± SEM; K and t1/2 mean and 95% CI"},{"pmid":"35708053","species":"rodent","arm":"","form":"Sofosbuvir + ledipasvir","forms":[],"dose":"40 SFB and 9 LED mg/kg","doseBasis":"NR","fed":"fasted ~12 h","n":"4","analyte":"GS-331007 (sofosbuvir metabolite)","matrix":"plasma","parameter":"AUC","detail":"AUC (model-fitted)","value":"10,673","variance":"± 763 (SEM)","units":"ng/ml h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table 4 footnote: AUC mean ± SEM; K and t1/2 mean and 95% CI"},{"pmid":"35708053","species":"rodent","arm":"","form":"Silymarin (SLY) with SFB and LED (NR (SLY 88% provided by Arab Company for Gelatin and Pharmaceutical Products))","forms":["silymarin"],"dose":"40 SFB, 9 LED, 30 SLY mg/kg","doseBasis":"NR","fed":"fasted ~12 h","n":"4","analyte":"GS-331007 (sofosbuvir metabolite)","matrix":"plasma","parameter":"AUC","detail":"AUC (model-fitted)","value":"7,657","variance":"± 774 (SEM)","units":"ng/ml h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table 4 footnote: AUC mean ± SEM; K and t1/2 mean and 95% CI"},{"pmid":"35708053","species":"rodent","arm":"","form":"Sofosbuvir + ledipasvir","forms":[],"dose":"40 SFB and 9 LED mg/kg","doseBasis":"NR","fed":"fasted ~12 h","n":"4","analyte":"ledipasvir","matrix":"plasma","parameter":"AUC","detail":"AUC (model-fitted)","value":"919.7","variance":"± 95.34 (SEM)","units":"ng/ml h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table 4 footnote: AUC mean ± SEM; K and t1/2 mean and 95% CI"},{"pmid":"35708053","species":"rodent","arm":"","form":"Silymarin (SLY) with SFB and LED (NR (SLY 88% provided by Arab Company for Gelatin and Pharmaceutical Products))","forms":["silymarin"],"dose":"40 SFB, 9 LED, 30 SLY mg/kg","doseBasis":"NR","fed":"fasted ~12 h","n":"4","analyte":"ledipasvir","matrix":"plasma","parameter":"AUC","detail":"AUC (model-fitted)","value":"1,081","variance":"± 71.18 (SEM)","units":"ng/ml h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Table 4 footnote: AUC mean ± SEM; K and t1/2 mean and 95% CI"},{"pmid":"35890088","species":"rodent","arm":"","form":"Silymarin (Yucca Enterprises, Mumbai) suspension (Yucca Enterprises)","forms":["silymarin"],"dose":"100 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.40","variance":"± 0.10 (SD)","units":"µg mL−1","location":"Table 5","quote":"","quoteCheck":"no quote","note":""},{"pmid":"35890088","species":"rodent","arm":"","form":"Silymarin-soybean phosphatidylcholine (Phospholipon 90G) complex, drug:phospholipid 1:1.93","forms":[],"dose":"~100 (silymarin equivalent) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.10","variance":"± 0.21 (SD)","units":"µg mL−1","location":"Table 5","quote":"","quoteCheck":"no quote","note":""},{"pmid":"35890088","species":"rodent","arm":"","form":"Silymarin (Yucca Enterprises, Mumbai) suspension (Yucca Enterprises)","forms":["silymarin"],"dose":"100 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"4.0","variance":"","units":"h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Tmax given without variance; statistic type not stated"},{"pmid":"35890088","species":"rodent","arm":"","form":"Silymarin-soybean phosphatidylcholine (Phospholipon 90G) complex, drug:phospholipid 1:1.93","forms":[],"dose":"~100 (silymarin equivalent) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"6.0","variance":"","units":"h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Tmax given without variance; statistic type not stated"},{"pmid":"35890088","species":"rodent","arm":"","form":"Silymarin (Yucca Enterprises, Mumbai) suspension (Yucca Enterprises)","forms":["silymarin"],"dose":"100 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"2.80","variance":"± 0.71 (SD)","units":"µg mL−1 h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Phytosome AUC0-t (45.76) is larger than its AUC0-∞ (22.33) as printed, which is internally inconsistent; Methods say AUC0-24h but samples only to 12 h"},{"pmid":"35890088","species":"rodent","arm":"","form":"Silymarin-soybean phosphatidylcholine (Phospholipon 90G) complex, drug:phospholipid 1:1.93","forms":[],"dose":"~100 (silymarin equivalent) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"45.76","variance":"± 1.41 (SD)","units":"µg mL−1 h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Phytosome AUC0-t (45.76) is larger than its AUC0-∞ (22.33) as printed, which is internally inconsistent; Methods say AUC0-24h but samples only to 12 h"},{"pmid":"35890088","species":"rodent","arm":"","form":"Silymarin (Yucca Enterprises, Mumbai) suspension (Yucca Enterprises)","forms":["silymarin"],"dose":"100 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"3.84","variance":"± 0.91 (SD)","units":"mL−1 h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Unit printed as 'mL−1 h' (no mass unit) on page image; no significance mark printed for phytosome AUC0-∞"},{"pmid":"35890088","species":"rodent","arm":"","form":"Silymarin-soybean phosphatidylcholine (Phospholipon 90G) complex, drug:phospholipid 1:1.93","forms":[],"dose":"~100 (silymarin equivalent) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"22.33","variance":"± 2.13 (SD)","units":"mL−1 h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Unit printed as 'mL−1 h' (no mass unit) on page image; no significance mark printed for phytosome AUC0-∞"},{"pmid":"35890088","species":"rodent","arm":"","form":"Silymarin-soybean phosphatidylcholine (Phospholipon 90G) complex, drug:phospholipid 1:1.93","forms":[],"dose":"~100 (silymarin equivalent) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"text value","value":"1.1 ± 0.12","variance":"± 0.12 (SD)","units":"µg/mL","location":"Results 2.10, p.13","quote":"Cmax = 1.1 ± 0.12 µg/mL","quoteCheck":"supported","note":"Inconsistent with Table 5 (1.10 ± 0.21)"},{"pmid":"35890088","species":"rodent","arm":"","form":"Silymarin (Yucca Enterprises, Mumbai) suspension (Yucca Enterprises)","forms":["silymarin"],"dose":"100 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"text value","value":"0.4 ± 0.10","variance":"± 0.10 (SD)","units":"µg/mL","location":"Results 2.10, p.13","quote":"Cmax = 0.4 ± 0.10 µg/mL","quoteCheck":"supported","note":"Matches Table 5 (0.40 ± 0.10)"},{"pmid":"35890088","species":"rodent","arm":"","form":"Silymarin-soybean phosphatidylcholine (Phospholipon 90G) complex, drug:phospholipid 1:1.93","forms":[],"dose":"~100 (silymarin equivalent) mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"relative_bioavailability","detail":"phytosome vs plain silymarin","value":"~6-fold","variance":"","units":"fold","location":"Abstract; Results 2.10, p.13","quote":"mean relative bioavailability of the optimized silymarin phytosomal formulation was ~6-fold that of the plain drug","quoteCheck":"supported","note":"Not tabulated; abstract says '6-fold increase in the systemic bioavailability'. Table 5 AUC values (0-t 45.76/2.80; 0-inf 22.33/3.84) do not give a consistent ratio; authors do not state which AUC was used"},{"pmid":"36178580","species":"rodent","arm":"","form":"Silymarin suspension in 0.5% CMC","forms":["silymarin"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"4","analyte":"silymarin flavolignans (sum)","matrix":"plasma","parameter":"Cmax","detail":"","value":"71.0","variance":"± 44.2 (SD)","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"36178580","species":"rodent","arm":"","form":"Silymarin-TPGS solid dispersion (prior formulation, Song et al. 2021)","forms":["enhanced"],"dose":"50 (as silymarin) mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"4","analyte":"silymarin flavolignans (sum)","matrix":"plasma","parameter":"Cmax","detail":"","value":"335.5","variance":"± 62.1 (SD)","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no 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overnight","n":"3","analyte":"silibinin","matrix":"plasma","parameter":"Tmax","detail":"Tmax","value":"0.0833","variance":"","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"i.v. dosing, so not an oral absorption value. Table 4 prints no variance for Tmax"},{"pmid":"37457888","species":"rodent","arm":"","form":"Synthetic silibinin glycosyl derivative 15","forms":[],"dose":"2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"3","analyte":"compound 15 (silibinin glycosyl derivative)","matrix":"plasma","parameter":"Tmax","detail":"Tmax","value":"0.0833","variance":"","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"i.v. dosing, so not an oral absorption value. Synthetic glycosylated derivative, not a natural milk thistle form. Table 4 prints no variance for Tmax"},{"pmid":"37457888","species":"rodent","arm":"","form":"Silibinin","forms":[],"dose":"2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"3","analyte":"silibinin","matrix":"plasma","parameter":"Cmax","detail":"Cmax","value":"633.0","variance":"± 19.7 (SD)","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":"i.v. dosing, so not an oral absorption value. +/- stated as SD in Fig. 5 caption (mean ± SD, n = 3); Table 4 does not state the variance type"},{"pmid":"37457888","species":"rodent","arm":"","form":"Synthetic silibinin glycosyl derivative 15","forms":[],"dose":"2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"3","analyte":"compound 15 (silibinin glycosyl derivative)","matrix":"plasma","parameter":"Cmax","detail":"Cmax","value":"373.0","variance":"± 75.4 (SD)","units":"ng/mL","location":"Table 4","quote":"","quoteCheck":"no quote","note":"i.v. dosing, so not an oral absorption value. Synthetic glycosylated derivative, not a natural milk thistle form. +/- stated as SD in Fig. 5 caption (mean ± SD, n = 3); Table 4 does not state the variance type"},{"pmid":"37457888","species":"rodent","arm":"","form":"Silibinin","forms":[],"dose":"2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"3","analyte":"silibinin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"175.0","variance":"± 5.0 (SD)","units":"ng/mL·h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"i.v. dosing, so not an oral absorption value. +/- stated as SD in Fig. 5 caption (mean ± SD, n = 3); Table 4 does not state the variance type"},{"pmid":"37457888","species":"rodent","arm":"","form":"Synthetic silibinin glycosyl derivative 15","forms":[],"dose":"2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"3","analyte":"compound 15 (silibinin glycosyl derivative)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"111.0","variance":"± 19.6 (SD)","units":"ng/mL·h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"i.v. dosing, so not an oral absorption value. Synthetic glycosylated derivative, not a natural milk thistle form. +/- stated as SD in Fig. 5 caption (mean ± SD, n = 3); Table 4 does not state the variance type"},{"pmid":"37774895","species":"rodent","arm":"","form":"Silybin (Sigma S0417) (Sigma-Aldrich)","forms":[],"dose":"120 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC at 24 h after treatment (Table 3 caption: 'at 24h'); interval start not stated","value":"55.45","variance":"± 11.78 (SEM)","units":"ng·ml−1·h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Silybin (SIY) rows of Table 3"},{"pmid":"37774895","species":"rodent","arm":"","form":"Physical mixture of berberine HCl and silybin","forms":[],"dose":"120 SIY (with 100 BBR) mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC at 24 h after treatment (Table 3 caption: 'at 24h'); interval start not stated","value":"198.9","variance":"± 64.4 (SEM)","units":"ng·ml−1·h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Silybin (SIY) rows of Table 3"},{"pmid":"37774895","species":"rodent","arm":"","form":"Berberine-silybin salt","forms":[],"dose":"120 SIY (with 100 BBR) mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC at 24 h after treatment (Table 3 caption: 'at 24h'); interval start not stated","value":"400.6","variance":"± 110.6 (SEM)","units":"ng·ml−1·h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Silybin (SIY) rows of Table 3"},{"pmid":"37774895","species":"rodent","arm":"","form":"Silybin (Sigma S0417) (Sigma-Aldrich)","forms":[],"dose":"120 mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"liver","parameter":"AUC","detail":"AUC at 24 h after treatment (liver tissue)","value":"3.372","variance":"± 2.086 (SEM)","units":"μg·g−1·h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Silybin (SIY) rows of Table 3"},{"pmid":"37774895","species":"rodent","arm":"","form":"Physical mixture of berberine HCl and silybin","forms":[],"dose":"120 SIY (with 100 BBR) mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"liver","parameter":"AUC","detail":"AUC at 24 h after treatment (liver tissue)","value":"5.254","variance":"± 5.872 (SEM)","units":"μg·g−1·h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Silybin (SIY) rows of Table 3"},{"pmid":"37774895","species":"rodent","arm":"","form":"Berberine-silybin salt","forms":[],"dose":"120 SIY (with 100 BBR) mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"liver","parameter":"AUC","detail":"AUC at 24 h after treatment (liver tissue)","value":"22.88","variance":"± 5.653 (SEM)","units":"μg·g−1·h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Silybin (SIY) rows of Table 3"},{"pmid":"37774895","species":"rodent","arm":"","form":"Berberine-silybin salt","forms":[],"dose":"120 SIY (with 100 BBR) mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"85.7","variance":"","units":"ng/ml","location":"Results 3.4","quote":"For SIY in BSS, the Cmax was increased to 85.7 ng/ml with an AUC of 10.72 ng⋅ml− 1⋅h at 0.5 h.","quoteCheck":"supported","note":"Text also prints 'AUC of 10.72 ng·ml−1·h at 0.5 h', which does not match the 24 h AUC of 400.6 in Table 3 (unclear interval); Tmax implied 0.5 h but not stated as such"},{"pmid":"37774895","species":"rodent","arm":"","form":"Berberine-silybin salt","forms":[],"dose":"120 SIY (with 100 BBR) mg/kg","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC printed in Results text at 0.5 h","value":"10.72","variance":"","units":"ng·ml−1·h","location":"Results 3.4","quote":"with an AUC of 10.72 ng⋅ml− 1⋅h at 0.5 h","quoteCheck":"supported","note":"Inconsistent with Table 3 plasma AUC of 400.6 ng·ml−1·h for BSS; interval not clear"},{"pmid":"38093834","species":"rodent","arm":"","form":"Liposome (DPPC/POPC-cholesterol-cholic acid) loaded with Sil, thin-film dispersion; PD < 130 nm, PDI < 0.3, negative zeta","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin (Sil)","matrix":"plasma","parameter":"Cmax","detail":"","value":"2217.43","variance":"± 159.95 (SD)","units":"ng/mL","location":"Results (Sil-Lip Enhanced the Oral Absorption of Sil)","quote":"the peak plasma concentration (Cmax), area under the curve (AUC), half-life (T1/2), and mean residence time (MRT) of Sil-Lip were 2217.43 ± 159.95 ng/mL, 9778.57 ± 901.39 ng/mL·h, 3.44 ± 0.72 h, and 5.18 ± 0.38 h","quoteCheck":"supported","note":"+/- as printed; variance type not stated in text (Fig. 1H caption: mean ± SD, n = 6). Free Sil absolute values are in Table S1 (Supporting Information, not in PDF)"},{"pmid":"38093834","species":"rodent","arm":"","form":"Liposome (DPPC/POPC-cholesterol-cholic acid) loaded with Sil, thin-film dispersion; PD < 130 nm, PDI < 0.3, negative zeta","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin (Sil)","matrix":"plasma","parameter":"AUC","detail":"AUC, interval NR (sampling to 24 h)","value":"9778.57","variance":"± 901.39 (SD)","units":"ng/mL·h","location":"Results (Sil-Lip Enhanced the Oral Absorption of Sil)","quote":"the peak plasma concentration (Cmax), area under the curve (AUC), half-life (T1/2), and mean residence time (MRT) of Sil-Lip were 2217.43 ± 159.95 ng/mL, 9778.57 ± 901.39 ng/mL·h, 3.44 ± 0.72 h, and 5.18 ± 0.38 h","quoteCheck":"supported","note":"+/- as printed; variance type not stated in text (Fig. 1H caption: mean ± SD, n = 6). Free Sil absolute values are in Table S1 (Supporting Information, not in PDF)"},{"pmid":"38093834","species":"rodent","arm":"","form":"Liposome (DPPC/POPC-cholesterol-cholic acid) loaded with Sil, thin-film dispersion; PD < 130 nm, PDI < 0.3, negative zeta","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silibinin (Sil)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative oral bioavailability, F = AUC Sil-Lip / AUC Sil × 100% (stated as 'times higher')","value":"9.45","variance":"","units":"times","location":"Results (Sil-Lip Enhanced the Oral Absorption of Sil)","quote":"the relative bioavailability of Sil-Lip was 9.45 times higher than that of the free Sil","quoteCheck":"supported","note":"Methods give F = AUC(Sil-Lip)/AUC(Sil) × 100%; text expresses result as '9.45 times higher'"},{"pmid":"38139990","species":"rodent","arm":"","form":"silybin-loaded bovine serum albumin nanoparticles (coacervation, PEG, glutaraldehyde crosslinked)","forms":["enhanced"],"dose":"1.5 mg/kg","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"184.10","variance":"","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Methods state data are mean +/- SD, but no variance printed in Table 3; route intranasal"},{"pmid":"38139990","species":"rodent","arm":"","form":"free silybin (aqueous solution)","forms":[],"dose":"1.5 mg/kg","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"101.4","variance":"","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"route intranasal; no variance printed"},{"pmid":"38139990","species":"rodent","arm":"","form":"silybin-loaded bovine serum albumin nanoparticles (coacervation, PEG, glutaraldehyde crosslinked)","forms":["enhanced"],"dose":"1.5 mg/kg","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"","units":"h","location":"Table 3","quote":"Both formulations exhibited a rapid attainment of peak plasma concentration within just 0.5 h","quoteCheck":"supported","note":""},{"pmid":"38139990","species":"rodent","arm":"","form":"free silybin (aqueous solution)","forms":[],"dose":"1.5 mg/kg","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38139990","species":"rodent","arm":"","form":"silybin-loaded bovine serum albumin nanoparticles (coacervation, PEG, glutaraldehyde crosslinked)","forms":["enhanced"],"dose":"1.5 mg/kg","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"921.89","variance":"","units":"ng·h/mL","location":"Table 3","quote":"the AUC0-24h value of BSA-NP/SLB was four times greater than that of the SLB solution (p < 0.05)","quoteCheck":"value not in quote","note":""},{"pmid":"38139990","species":"rodent","arm":"","form":"free silybin (aqueous solution)","forms":[],"dose":"1.5 mg/kg","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"218.17","variance":"","units":"ng·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38139990","species":"rodent","arm":"","form":"silybin-loaded bovine serum albumin nanoparticles (coacervation, PEG, glutaraldehyde crosslinked)","forms":["enhanced"],"dose":"1.5 mg/kg","doseBasis":"active compound","fed":"NR","n":"7","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"fold increase in AUC0-24h vs free SLB (author statement, intranasal)","value":"fourfold","variance":"","units":"fold","location":"Abstract; Results 3.4","quote":"improved SLB bioavailability by fourfold compared to free SLB","quoteCheck":"supported","note":"Author wording; no ratio or CI printed"},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.50","variance":"± 0.18 (SD)","units":"µM","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-4h","value":"0.36","variance":"","units":"µM·h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"silybin A","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.25","variance":"± 0.25−1 (range)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"silybin A","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.72","variance":"± 1.11 (SD)","units":"µM","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"silybin A","matrix":"plasma","parameter":"AUC","detail":"AUC0-4h","value":"0.92","variance":"","units":"µM·h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"silybin A","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.25","variance":"± 0.25−1 (range)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.59","variance":"± 0.25 (SD)","units":"µM","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active 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and returned 2 h post-gavage","n":"6","analyte":"silybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"2.05","variance":"± 1.39 (SD)","units":"µM","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"silybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-4h","value":"1.15","variance":"","units":"µM·h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h 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B","matrix":"plasma","parameter":"AUC","detail":"AUC0-4h","value":"0.14","variance":"","units":"µM·h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"isosilybin B","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.25","variance":"± 0.25−1 (range)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"isosilybin B","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.44","variance":"± 0.29 (SD)","units":"µM","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"isosilybin B","matrix":"plasma","parameter":"AUC","detail":"AUC0-4h","value":"1.97","variance":"","units":"µM·h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Printed value 1.97 lies outside its printed 90% CI (0.07−0.54); recorded as printed, possible typo in paper (not resolved)"},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"isosilybin B","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.25","variance":"± 0.25−1 (range)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"silychristin","matrix":"plasma","parameter":"Cmax","detail":"","value":"<LOQ","variance":"","units":"µM","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Below lower limit of quantification (LLOQ 2 nM); AUC, tmax, t1/2 ND"},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"silychristin","matrix":"plasma","parameter":"Cmax","detail":"","value":"<LOQ","variance":"","units":"µM","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Below lower limit of quantification (LLOQ 2 nM); AUC, tmax, t1/2 ND"},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"isosilychristin","matrix":"plasma","parameter":"Cmax","detail":"","value":"<LOQ","variance":"","units":"µM","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Below LLOQ; AUC, tmax, t1/2 ND"},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"isosilychristin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.07","variance":"± 0.03 (SD)","units":"µM","location":"Table 1","quote":"","quoteCheck":"no quote","note":"AUC, tmax, t1/2 ND"},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (milk thistle extract) (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"1000 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"2","analyte":"silybin A","matrix":"plasma","parameter":"Cmax","detail":"preliminary study, 1000 mg/kg silymarin","value":"10.7","variance":"","units":"µM","location":"Discussion p.2293","quote":"yielded silybin A Cmax values of 10.7 µM in the OATP1B mice","quoteCheck":"supported","note":"Preliminary n=2 study; no variance; no other detail printed"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle + pitavastatin (PIT)","forms":[],"dose":"5 mg/kg PIT","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6 (Methods); Table 2 title FVB n = 4","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-12h","value":"77.3","variance":"","units":"nM·h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin), reported as interaction context"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle + pitavastatin (PIT)","forms":[],"dose":"5 mg/kg PIT","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6 (Methods); Table 2 title FVB n = 4","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Cmax","detail":"","value":"31.6","variance":"± 22.8 (SD)","units":"nM","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin)"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle + pitavastatin (PIT)","forms":[],"dose":"5 mg/kg PIT","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6 (Methods); Table 2 title FVB n = 4","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.8","variance":"± 0.7 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin). Caption says tmax is median (range) but a single value in parentheses is printed; recorded as printed, variance type unclear"},{"pmid":"38529622","species":"rodent","arm":"","form":"pitavastatin + silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"5 (PIT) + 500 (silymarin) mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6 (Methods); Table 2 title FVB n = 4","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-12h","value":"68.9","variance":"","units":"nM·h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin), reported as interaction context"},{"pmid":"38529622","species":"rodent","arm":"","form":"pitavastatin + silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"5 (PIT) + 500 (silymarin) mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6 (Methods); Table 2 title FVB n = 4","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Cmax","detail":"","value":"34.0","variance":"± 14.4 (SD)","units":"nM","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin)"},{"pmid":"38529622","species":"rodent","arm":"","form":"pitavastatin + silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"5 (PIT) + 500 (silymarin) mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6 (Methods); Table 2 title FVB n = 4","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"± 0.0 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin). Caption says tmax is median (range) but a single value in parentheses is printed; recorded as printed, variance type unclear"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle + pitavastatin (PIT)","forms":[],"dose":"5 mg/kg PIT","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-12h","value":"614.4","variance":"","units":"nM·h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin), reported as interaction context"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle + pitavastatin (PIT)","forms":[],"dose":"5 mg/kg PIT","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Cmax","detail":"","value":"217.7","variance":"± 118.2 (SD)","units":"nM","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin)"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle + pitavastatin (PIT)","forms":[],"dose":"5 mg/kg PIT","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.9","variance":"± 0.8 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin). Caption says tmax is median (range) but a single value in parentheses is printed; recorded as printed, variance type unclear"},{"pmid":"38529622","species":"rodent","arm":"","form":"pitavastatin + silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"5 (PIT) + 500 (silymarin) mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-12h","value":"1159.7","variance":"","units":"nM·h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin), reported as interaction context"},{"pmid":"38529622","species":"rodent","arm":"","form":"pitavastatin + silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"5 (PIT) + 500 (silymarin) mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Cmax","detail":"","value":"579.2","variance":"± 313.8 (SD)","units":"nM","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin); Table 2 marks * (p<0.05) vs vehicle"},{"pmid":"38529622","species":"rodent","arm":"","form":"pitavastatin + silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"5 (PIT) + 500 (silymarin) mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pitavastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"± 0.1 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin). Caption says tmax is median (range) but a single value in parentheses is printed; recorded as printed, variance type unclear"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle + pravastatin (PRV)","forms":[],"dose":"20 mg/kg PRV","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"4 (Methods, Fig. 3); Table 3 title FVB n = 6","analyte":"pravastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-2h","value":"24.7","variance":"","units":"nM·h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin)"},{"pmid":"38529622","species":"rodent","arm":"","form":"pravastatin + silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"20 (PRV) + 500 (silymarin) mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"4 (Methods, Fig. 3); Table 3 title FVB n = 6","analyte":"pravastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-2h","value":"43.7","variance":"","units":"nM·h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin)"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle + pravastatin (PRV)","forms":[],"dose":"20 mg/kg PRV","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"4 (Methods, Fig. 3); Table 3 title FVB n = 6","analyte":"pravastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"nM","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte; ND (not determined); text: Cmax in FVB not reported due to longer absorption phase than anticipated"},{"pmid":"38529622","species":"rodent","arm":"","form":"pravastatin + silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"20 (PRV) + 500 (silymarin) mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"4 (Methods, Fig. 3); Table 3 title FVB n = 6","analyte":"pravastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Cmax","detail":"","value":"ND","variance":"","units":"nM","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte; ND (not determined); text: Cmax in FVB not reported due to longer absorption phase than anticipated"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle + pravastatin (PRV)","forms":[],"dose":"20 mg/kg PRV","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pravastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-2h","value":"755.3","variance":"","units":"nM·h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin)"},{"pmid":"38529622","species":"rodent","arm":"","form":"pravastatin + silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"20 (PRV) + 500 (silymarin) mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pravastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-2h","value":"1353.4","variance":"","units":"nM·h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin)"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle + pravastatin (PRV)","forms":[],"dose":"20 mg/kg PRV","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pravastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Cmax","detail":"","value":"412.9","variance":"± 63.2 (SD)","units":"nM","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin)"},{"pmid":"38529622","species":"rodent","arm":"","form":"pravastatin + silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"20 (PRV) + 500 (silymarin) mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pravastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Cmax","detail":"","value":"786.1","variance":"± 306.2 (SD)","units":"nM","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin); Table 3 marks * (p<0.05) vs vehicle"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle + pravastatin (PRV)","forms":[],"dose":"20 mg/kg PRV","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pravastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Tmax","detail":"","value":"75","variance":"± 15−120 (range)","units":"min","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin)"},{"pmid":"38529622","species":"rodent","arm":"","form":"pravastatin + silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"20 (PRV) + 500 (silymarin) mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"pravastatin (co-administered probe; silymarin as inhibitor)","matrix":"plasma","parameter":"Tmax","detail":"","value":"60","variance":"± 30−120 (range)","units":"min","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Off-target analyte (statin)"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle","forms":[],"dose":"NR NR","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"coproporphyrin-I (OATP1B biomarker; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"2.8","variance":"","units":"nM·h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Off-target analyte (endogenous biomarker)"},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"coproporphyrin-I (OATP1B biomarker; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"2.5","variance":"","units":"nM·h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Off-target analyte (endogenous biomarker)"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle","forms":[],"dose":"NR NR","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"coproporphyrin-I (OATP1B biomarker; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"4.4","variance":"","units":"nM·h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Off-target analyte (endogenous biomarker)"},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"coproporphyrin-I (OATP1B biomarker; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"4.4","variance":"","units":"nM·h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Off-target analyte (endogenous biomarker)"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle","forms":[],"dose":"NR NR","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6 (Methods); Table 5 title FVB n = 4","analyte":"coproporphyrin-III (OATP1B biomarker; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"7.2","variance":"","units":"nM·h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Off-target analyte (endogenous biomarker)"},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6 (Methods); Table 5 title FVB n = 4","analyte":"coproporphyrin-III (OATP1B biomarker; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"8.2","variance":"","units":"nM·h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Off-target analyte (endogenous biomarker)"},{"pmid":"38529622","species":"rodent","arm":"","form":"vehicle","forms":[],"dose":"NR NR","doseBasis":"NR","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"coproporphyrin-III (OATP1B biomarker; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"10.5","variance":"","units":"nM·h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Off-target analyte (endogenous biomarker)"},{"pmid":"38529622","species":"rodent","arm":"","form":"silymarin (Madaus AG (Cologne, Germany) silymarin extract)","forms":["silymarin"],"dose":"500 mg/kg","doseBasis":"active compound","fed":"Food removed 4 h before gavage and returned 2 h post-gavage","n":"6","analyte":"coproporphyrin-III (OATP1B biomarker; silymarin as inhibitor)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"11.8","variance":"","units":"nM·h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Off-target analyte (endogenous biomarker)"},{"pmid":"39370820","species":"rodent","arm":"","form":"silybin liposome modified with DSPE-PEG-MyrB and DSPE-PEG2000-LC","forms":["enhanced"],"dose":"300 µg/mL x 300 µL injection as printed","doseBasis":"active compound","fed":"NR","n":"5 per time point","analyte":"silybin","matrix":"liver","parameter":"AUC","detail":"AUC of silybin in liver (trapezoid, mouse IV)","value":"66.5","variance":"","units":"mg*h/L","location":"Results 3.6 p.4920; Fig. 12B","quote":"The AUC of MyrB/LC Lip@SB in the liver was 66.5, almost twice that of Inj@SB (Figure 12B).","quoteCheck":"supported","note":"Units taken from Fig. 12B y-axis label (AUC(mg*h/L)); text gives no units. AUC interval not stated in text. Inj@SB liver value not given in text."},{"pmid":"39418531","species":"rodent","arm":"","form":"in-house DOX·HCl aqueous solution","forms":[],"dose":"15 mg/kg (DOX-equivalent)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"doxorubicin (DOX)","matrix":"plasma","parameter":"Cmax","detail":"","value":"72.53","variance":"","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table caption says mean ± SD but no SD printed in table."},{"pmid":"39418531","species":"rodent","arm":"","form":"aqueous suspension of silybin and DOX·HCl","forms":[],"dose":"15 mg/kg (DOX-equivalent)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"doxorubicin (DOX)","matrix":"plasma","parameter":"Cmax","detail":"","value":"81.93","variance":"","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table caption says mean ± SD but no SD printed in table."},{"pmid":"39418531","species":"rodent","arm":"","form":"silybin-conjugated chitosan micelles loaded with DOX","forms":["enhanced"],"dose":"15 mg/kg (DOX-equivalent)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"doxorubicin (DOX)","matrix":"plasma","parameter":"Cmax","detail":"","value":"291.42","variance":"","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table caption says mean ± SD but no SD printed in table."},{"pmid":"39418531","species":"rodent","arm":"","form":"in-house DOX·HCl aqueous solution","forms":[],"dose":"15 mg/kg (DOX-equivalent)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"doxorubicin (DOX)","matrix":"plasma","parameter":"Tmax","detail":"","value":"8","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Statistic type for Tmax not stated; table caption says mean ± SD but no SD printed."},{"pmid":"39418531","species":"rodent","arm":"","form":"aqueous suspension of silybin and DOX·HCl","forms":[],"dose":"15 mg/kg (DOX-equivalent)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"doxorubicin (DOX)","matrix":"plasma","parameter":"Tmax","detail":"","value":"8","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Statistic type for Tmax not stated; table caption says mean ± SD but no SD printed."},{"pmid":"39418531","species":"rodent","arm":"","form":"silybin-conjugated chitosan micelles loaded with DOX","forms":["enhanced"],"dose":"15 mg/kg (DOX-equivalent)","doseBasis":"active compound","fed":"fasted 12 h","n":"5","analyte":"doxorubicin (DOX)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Statistic type for Tmax not stated; table caption says mean ± SD but no SD 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1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39498271","species":"rodent","arm":"","form":"stabilizer-free silymarin nanocrystals (high-pressure homogenization), oral suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1585.70","variance":"± 213.98 (SD)","units":"µg·L−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39498271","species":"rodent","arm":"","form":"silymarin crude drug suspension, oral","forms":["silymarin"],"dose":"50 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"698.46","variance":"± 152.92 (SD)","units":"µg·L−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39498271","species":"rodent","arm":"","form":"silymarin dissolved in anhydrous ethanol, intravenous (tail vein)","forms":["silymarin"],"dose":"4 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"15,529.12","variance":"± 5763.62 (SD)","units":"µg·L−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39498271","species":"rodent","arm":"","form":"stabilizer-free silymarin nanocrystals (high-pressure homogenization), oral suspension","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.00","variance":"± 0.00 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39498271","species":"rodent","arm":"","form":"silymarin crude drug suspension, oral","forms":["silymarin"],"dose":"50 mg/kg","doseBasis":"NR","fed":"NR","n":"5","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.19","variance":"± 0.55 (SD)","units":"h","location":"Table 1","quote":"","quoteCheck":"no 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(freeze-dried)","forms":["silymarin"],"dose":"70 mg/kg","doseBasis":"NR","fed":"fasted (no food before dosing, water ad libitum)","n":"6 per Methods; 3 per Fig. 12 legend","analyte":"silymarin (SMN)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.1","variance":"± 0.6 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"n NR in table (Methods n=6, Fig. 12 n=3)."},{"pmid":"39567122","species":"rodent","arm":"","form":"sulfhydryl-modified β-cyclodextrin-silymarin inclusion complex (microwave-assisted, freeze-dried)","forms":["silymarin"],"dose":"70 mg/kg","doseBasis":"NR","fed":"fasted (no food before dosing, water ad libitum)","n":"6 per Methods; 3 per Fig. 12 legend","analyte":"silymarin (SMN)","matrix":"plasma","parameter":"Tmax","detail":"","value":"3.0","variance":"± 0.4 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"n NR in table (Methods n=6, Fig. 12 n=3)."},{"pmid":"39567122","species":"rodent","arm":"","form":"free silymarin suspension","forms":["silymarin"],"dose":"70 mg/kg","doseBasis":"NR","fed":"fasted (no food before dosing, water ad libitum)","n":"6 per Methods; 3 per Fig. 12 legend","analyte":"silymarin (SMN)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.25","variance":"± 0.04 (SD)","units":"µg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"n NR in table (Methods n=6, Fig. 12 n=3)."},{"pmid":"39567122","species":"rodent","arm":"","form":"β-cyclodextrin-silymarin inclusion complex (freeze-dried)","forms":["silymarin"],"dose":"70 mg/kg","doseBasis":"NR","fed":"fasted (no food before dosing, water ad libitum)","n":"6 per Methods; 3 per Fig. 12 legend","analyte":"silymarin (SMN)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.07","variance":"± 0.04 (SD)","units":"µg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"n NR in table (Methods n=6, Fig. 12 n=3)."},{"pmid":"39567122","species":"rodent","arm":"","form":"sulfhydryl-modified β-cyclodextrin-silymarin inclusion complex (microwave-assisted, freeze-dried)","forms":["silymarin"],"dose":"70 mg/kg","doseBasis":"NR","fed":"fasted (no food before dosing, water ad libitum)","n":"6 per Methods; 3 per Fig. 12 legend","analyte":"silymarin (SMN)","matrix":"plasma","parameter":"Cmax","detail":"","value":"2.5","variance":"± 0.43 (SD)","units":"µg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"n NR in table (Methods n=6, Fig. 12 n=3)."},{"pmid":"39567122","species":"rodent","arm":"","form":"free silymarin suspension","forms":["silymarin"],"dose":"70 mg/kg","doseBasis":"NR","fed":"fasted (no food before dosing, water ad libitum)","n":"6 per Methods; 3 per Fig. 12 legend","analyte":"silymarin (SMN)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"20.8","variance":"± 1.8 (SD)","units":"µg/mL*h","location":"Table 2","quote":"","quoteCheck":"no 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18.9 (SD)","units":"µg/mL*h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"n NR in table (Methods n=6, Fig. 12 n=3)."},{"pmid":"39567122","species":"rodent","arm":"","form":"free silymarin suspension","forms":["silymarin"],"dose":"70 mg/kg","doseBasis":"NR","fed":"fasted (no food before dosing, water ad libitum)","n":"6 per Methods; 3 per Fig. 12 legend","analyte":"silymarin (SMN)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr (%) as labelled; Methods Eq. 4 computes it from AUC oral/AUC IV with dose correction","value":"4.32","variance":"","units":"%","location":"Table 2; Results 3.10","quote":"","quoteCheck":"no quote","note":"Labelled relative bioavailability but formula references IV AUC."},{"pmid":"39567122","species":"rodent","arm":"","form":"β-cyclodextrin-silymarin inclusion complex (freeze-dried)","forms":["silymarin"],"dose":"70 mg/kg","doseBasis":"NR","fed":"fasted (no food before dosing, water ad libitum)","n":"6 per Methods; 3 per Fig. 12 legend","analyte":"silymarin (SMN)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr (%) as labelled; Methods Eq. 4 computes it from AUC oral/AUC IV with dose correction","value":"12.98","variance":"","units":"%","location":"Table 2; Results 3.10","quote":"","quoteCheck":"no quote","note":"Labelled relative bioavailability but formula references IV AUC."},{"pmid":"39567122","species":"rodent","arm":"","form":"sulfhydryl-modified β-cyclodextrin-silymarin inclusion complex (microwave-assisted, freeze-dried)","forms":["silymarin"],"dose":"70 mg/kg","doseBasis":"NR","fed":"fasted (no food before dosing, water ad libitum)","n":"6 per Methods; 3 per Fig. 12 legend","analyte":"silymarin (SMN)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr (%) as labelled; Methods Eq. 4 computes it from AUC oral/AUC IV with dose correction","value":"39.15","variance":"","units":"%","location":"Table 2; Results 3.10","quote":"","quoteCheck":"no 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Table 2 footnote IV AUC given as 481.4 µg/mL.h at 50 mg/kg."},{"pmid":"39567122","species":"rodent","arm":"","form":"silymarin in sterile 10 mM PBS pH 7.4, intravenous","forms":["silymarin"],"dose":"70 (Methods) / 50 (Table 2 footnote) mg/kg","doseBasis":"NR","fed":"fasted (no food before dosing, water ad libitum)","n":"6 per Methods; 3 per Fig. 12 legend","analyte":"silymarin (SMN)","matrix":"plasma","parameter":"AUC","detail":"AUC after IV administration (Table 2 footnote)","value":"481.4","variance":"± 57.4 (SD)","units":"µg/mL. h","location":"Table 2 footnote","quote":"AUC of SMN after i.v. administration of 50 mg/kg body weight was 481.4 ± 57.4 μg/mL. h.","quoteCheck":"supported","note":"Dose stated here as 50 mg/kg vs 70 mg/kg in Methods. Unit printed as 'µg/mL. h'."},{"pmid":"39567122","species":"rodent","arm":"","form":"free silymarin suspension","forms":["silymarin"],"dose":"70 mg/kg","doseBasis":"NR","fed":"fasted (no food before dosing, water ad libitum)","n":"6 per Methods; 3 per Fig. 12 legend","analyte":"silymarin (SMN)","matrix":"plasma","parameter":"Cmax","detail":"text statement of free SMN Cmax","value":"0.25","variance":"","units":"μg/mL","location":"Results 3.10 p.8","quote":"Silymarin exhibited poor drug absorption after oral administration (Cmax 0.25 μg/mL)","quoteCheck":"supported","note":""},{"pmid":"39861153","species":"rodent","arm":"","form":"raw silybin (purity >95%) dispersed in soybean oil","forms":[],"dose":"50 mg/kg (equivalent to silybin)","doseBasis":"active compound","fed":"overnight fast; feed resumed 4 h post-dose","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.17","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"No variance printed; statistic type not stated."},{"pmid":"39861153","species":"rodent","arm":"","form":"SILIPHOS (about 30% silybin) dispersed in soybean oil","forms":["phytosome"],"dose":"50 mg/kg (equivalent to silybin)","doseBasis":"active compound","fed":"overnight fast; feed resumed 4 h post-dose","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.17","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"No variance printed; statistic type not stated."},{"pmid":"39861153","species":"rodent","arm":"","form":"silybin-L-proline cocrystal (1:2 ratio) dispersed in soybean oil","forms":[],"dose":"50 mg/kg (equivalent to silybin)","doseBasis":"active compound","fed":"overnight fast; feed resumed 4 h post-dose","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.17","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"No variance printed; statistic type not stated."},{"pmid":"39861153","species":"rodent","arm":"","form":"raw silybin (purity >95%) dispersed in soybean oil","forms":[],"dose":"50 mg/kg (equivalent to silybin)","doseBasis":"active compound","fed":"overnight fast; feed resumed 4 h post-dose","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"137.94","variance":"± 49.29 (SD)","units":"ng·mL−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39861153","species":"rodent","arm":"","form":"SILIPHOS (about 30% silybin) dispersed in soybean oil","forms":["phytosome"],"dose":"50 mg/kg (equivalent to silybin)","doseBasis":"active compound","fed":"overnight fast; feed resumed 4 h post-dose","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1120.17","variance":"± 588.94 (SD)","units":"ng·mL−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39861153","species":"rodent","arm":"","form":"silybin-L-proline cocrystal (1:2 ratio) dispersed in soybean oil","forms":[],"dose":"50 mg/kg (equivalent to silybin)","doseBasis":"active compound","fed":"overnight fast; feed resumed 4 h post-dose","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"2257.33","variance":"± 914.51 (SD)","units":"ng·mL−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39861153","species":"rodent","arm":"","form":"raw silybin (purity >95%) dispersed in soybean oil","forms":[],"dose":"50 mg/kg (equivalent to silybin)","doseBasis":"active compound","fed":"overnight fast; feed resumed 4 h post-dose","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h","value":"88.55","variance":"± 16.46 (SD)","units":"ng·h·mL−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39861153","species":"rodent","arm":"","form":"SILIPHOS (about 30% silybin) dispersed in soybean oil","forms":["phytosome"],"dose":"50 mg/kg (equivalent to silybin)","doseBasis":"active compound","fed":"overnight fast; feed resumed 4 h post-dose","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h","value":"569.21","variance":"± 236.93 (SD)","units":"ng·h·mL−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39861153","species":"rodent","arm":"","form":"silybin-L-proline cocrystal (1:2 ratio) dispersed in soybean oil","forms":[],"dose":"50 mg/kg (equivalent to silybin)","doseBasis":"active compound","fed":"overnight fast; feed resumed 4 h post-dose","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h","value":"1431.94","variance":"± 882.80 (SD)","units":"ng·h·mL−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39861153","species":"rodent","arm":"","form":"SILIPHOS (about 30% silybin) dispersed in soybean oil","forms":["phytosome"],"dose":"50 mg/kg (equivalent to silybin)","doseBasis":"active compound","fed":"overnight fast; feed resumed 4 h post-dose","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"AUC0-8h ratio vs raw silybin (authors' statement, fold)","value":"6.4","variance":"","units":"fold","location":"Results 2.8 p.6","quote":"","quoteCheck":"no quote","note":""},{"pmid":"39861153","species":"rodent","arm":"","form":"silybin-L-proline cocrystal (1:2 ratio) dispersed in soybean oil","forms":[],"dose":"50 mg/kg (equivalent to silybin)","doseBasis":"active compound","fed":"overnight fast; feed resumed 4 h post-dose","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"AUC0-8h ratio vs raw silybin (authors' statement, fold)","value":"16.2","variance":"","units":"fold","location":"Results 2.8 p.6","quote":"","quoteCheck":"no quote","note":"Abstract states cocrystal '16-fold increase in bioavailability'."},{"pmid":"40493802","species":"rodent","arm":"","form":"silybin suspended in 0.3% aq. CMC-Na","forms":[],"dose":"150 mg/kg","doseBasis":"active compound","fed":"overnight fasted","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"494.23","variance":"± 129.46 (SD)","units":"ng/mL h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"40493802","species":"rodent","arm":"","form":"A2, semisynthetic C-23 mercapto-silybin derivative, suspended in 0.3% aq. CMC-Na","forms":[],"dose":"150 mg/kg","doseBasis":"active compound","fed":"overnight fasted","n":"5","analyte":"A2 (silybin derivative)","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"11599.60","variance":"± 1758.88 (SD)","units":"ng/mL h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Analyte is derivative A2, not silybin."},{"pmid":"40493802","species":"rodent","arm":"","form":"silybin suspended in 0.3% aq. CMC-Na","forms":[],"dose":"150 mg/kg","doseBasis":"active compound","fed":"overnight fasted","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.02","variance":"± 0.05 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"40493802","species":"rodent","arm":"","form":"A2, semisynthetic C-23 mercapto-silybin derivative, suspended in 0.3% aq. CMC-Na","forms":[],"dose":"150 mg/kg","doseBasis":"active compound","fed":"overnight fasted","n":"5","analyte":"A2 (silybin derivative)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.99","variance":"± 0.03 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Analyte is derivative A2, not silybin."},{"pmid":"40493802","species":"rodent","arm":"","form":"silybin suspended in 0.3% aq. CMC-Na","forms":[],"dose":"150 mg/kg","doseBasis":"active compound","fed":"overnight fasted","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"194.34","variance":"± 23.06 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"40493802","species":"rodent","arm":"","form":"A2, semisynthetic C-23 mercapto-silybin derivative, suspended in 0.3% aq. CMC-Na","forms":[],"dose":"150 mg/kg","doseBasis":"active compound","fed":"overnight fasted","n":"5","analyte":"A2 (silybin derivative)","matrix":"plasma","parameter":"Cmax","detail":"","value":"4081.01","variance":"± 855.28 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Analyte is derivative A2, not silybin."},{"pmid":"40685047","species":"rodent","arm":"","form":"Free silibinin (solution/suspension per methods)","forms":[],"dose":"10 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"SLB","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"4.29","variance":"± 0.25 (SD)","units":"mg/L","location":"Table 1","quote":"Cmax mg/L 4.29 ± 0.25 4.79 ± 0.06 5.39 ± 0.34*","quoteCheck":"supported","note":""},{"pmid":"40685047","species":"rodent","arm":"","form":"Silibinin-hyaluronic acid conjugate nanoparticles (ester-linked prodrug, dialysis self-assembly)","forms":["enhanced"],"dose":"10 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"SLB","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"4.79","variance":"± 0.06 (SD)","units":"mg/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"40685047","species":"rodent","arm":"","form":"Chitosan-coated silibinin-hyaluronic acid conjugate nanoparticles","forms":["enhanced"],"dose":"10 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"SLB","matrix":"rat plasma","parameter":"Cmax","detail":"","value":"5.39","variance":"± 0.34 (SD)","units":"mg/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Asterisk footnote"},{"pmid":"40685047","species":"rodent","arm":"","form":"Free silibinin (solution/suspension per methods)","forms":[],"dose":"10 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"SLB","matrix":"rat plasma","parameter":"AUC","detail":"AUC0→∞","value":"10.52","variance":"± 1.99 (SD)","units":"h•mg/L","location":"Table 1","quote":"AUC0→∞ h•mg/L 10.52 ± 1.99 12.57 ± 1.16 16.71 ± 1.28*","quoteCheck":"supported","note":""},{"pmid":"40685047","species":"rodent","arm":"","form":"Silibinin-hyaluronic acid conjugate nanoparticles (ester-linked prodrug, dialysis self-assembly)","forms":["enhanced"],"dose":"10 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"SLB","matrix":"rat plasma","parameter":"AUC","detail":"AUC0→∞","value":"12.57","variance":"± 1.16 (SD)","units":"h•mg/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"40685047","species":"rodent","arm":"","form":"Chitosan-coated silibinin-hyaluronic acid conjugate nanoparticles","forms":["enhanced"],"dose":"10 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"SLB","matrix":"rat plasma","parameter":"AUC","detail":"AUC0→∞","value":"16.71","variance":"± 1.28 (SD)","units":"h•mg/L","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Asterisk footnote"},{"pmid":"42264004","species":"rodent","arm":"","form":"silybin-7-eicosanedioate prodrug suspension, intramuscular, posterior thigh (self-prepared)","forms":[],"dose":"135.00 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"326.85","variance":"± 34.18 (SD)","units":"g/L·h (as printed in Table 11; text says μg/mL·h)","location":"Table 11","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42264004","species":"rodent","arm":"","form":"capsule, oral gavage (Named 'Silibinin Capsules' in Table 11/Fig. 12 and 'Shuilinjia Capsule' (Shuilinjia, 35 mg tablets in Methods 2.1) in text)","forms":[],"dose":"18.90 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"22.43","variance":"± 0.44 (SD)","units":"g/L·h (as printed in Table 11; text says μg/mL·h)","location":"Table 11","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42264004","species":"rodent","arm":"","form":"silybin-7-eicosanedioate prodrug suspension, intramuscular, posterior thigh (self-prepared)","forms":[],"dose":"135.00 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"430.55","variance":"± 65.16 (SD)","units":"g/L·h (as printed in Table 11; text says μg/mL·h)","location":"Table 11","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42264004","species":"rodent","arm":"","form":"capsule, oral gavage (Named 'Silibinin Capsules' in Table 11/Fig. 12 and 'Shuilinjia Capsule' (Shuilinjia, 35 mg tablets in Methods 2.1) in text)","forms":[],"dose":"18.90 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"23.79","variance":"± 1.21 (SD)","units":"g/L·h (as printed in Table 11; text says μg/mL·h)","location":"Table 11","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42264004","species":"rodent","arm":"","form":"silybin-7-eicosanedioate prodrug suspension, intramuscular, posterior thigh (self-prepared)","forms":[],"dose":"135.00 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"Tmax","detail":"","value":"9.00","variance":"± 4.24 (SD)","units":"h","location":"Table 11","quote":"","quoteCheck":"no quote","note":"Table 11 gives mean ± SD (not median)"},{"pmid":"42264004","species":"rodent","arm":"","form":"capsule, oral gavage (Named 'Silibinin Capsules' in Table 11/Fig. 12 and 'Shuilinjia Capsule' (Shuilinjia, 35 mg tablets in Methods 2.1) in text)","forms":[],"dose":"18.90 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.25","variance":"± 0.00 (SD)","units":"h","location":"Table 11","quote":"","quoteCheck":"no quote","note":"Table 11 gives mean ± SD (not median)"},{"pmid":"42264004","species":"rodent","arm":"","form":"silybin-7-eicosanedioate prodrug suspension, intramuscular, posterior thigh (self-prepared)","forms":[],"dose":"135.00 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.08","variance":"± 0.50 (SD)","units":"g/L (as printed in Table 11; text says μg/mL)","location":"Table 11","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42264004","species":"rodent","arm":"","form":"capsule, oral gavage (Named 'Silibinin Capsules' in Table 11/Fig. 12 and 'Shuilinjia Capsule' (Shuilinjia, 35 mg tablets in Methods 2.1) in text)","forms":[],"dose":"18.90 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"Cmax","detail":"","value":"11.65","variance":"± 4.35 (SD)","units":"g/L (as printed in Table 11; text says μg/mL)","location":"Table 11","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42264004","species":"rodent","arm":"","form":"silybin-7-eicosanedioate prodrug suspension, intramuscular, posterior thigh (self-prepared)","forms":[],"dose":"135.00 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"","value":"613.60","variance":"","units":"%","location":"Table 11; Abstract; Section 3.8","quote":"exhibited a 613.60% higher relative bioavailability compared with the Shuilinjia® Capsules group","quoteCheck":"supported","note":"Text (Section 3.8) says '613.60% higher' while Table 11 lists 613.60 as relative bioavailability; abstract says 'relative bioavailability of 613.60%'. Comparator named Silibinin Group in Table 11 but Shuilinjia Capsules in text. Basis (AUC type, dose normalisation) not stated."},{"pmid":"42264004","species":"rodent","arm":"","form":"silybin-7-eicosanedioate prodrug suspension, intramuscular, posterior thigh (self-prepared)","forms":[],"dose":"135.00 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"Cmax","detail":"text value (Section 3.8)","value":"1080","variance":"± 500 (SD)","units":"μg/mL","location":"Results Section 3.8 (p.18)","quote":"lower maximum plasma concentration (Cmax = 1080 ± 500 μg/mL)","quoteCheck":"supported","note":"Same value as Table 11 (1.08 ± 0.50 g/L) expressed in text as 1080 ± 500 μg/mL; unit printed differs between table and text"},{"pmid":"42264004","species":"rodent","arm":"","form":"silybin-7-eicosanedioate prodrug suspension, intramuscular, posterior thigh (self-prepared)","forms":[],"dose":"135.00 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t text","value":"326.850","variance":"± 34.180 (SD)","units":"μg/mL·h","location":"Results Section 3.8 (p.18)","quote":"AUC(0–t) and AUC(0–∞) values of 326.850 ± 34.180 μg/mL⋅h and 430.550 ± 65.160 μg/mL⋅h","quoteCheck":"supported","note":"Text unit μg/mL·h; Table 11 prints g/L·h"},{"pmid":"42264004","species":"rodent","arm":"","form":"silybin-7-eicosanedioate prodrug suspension, intramuscular, posterior thigh (self-prepared)","forms":[],"dose":"135.00 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silybin (SLB)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf text","value":"430.550","variance":"± 65.160 (SD)","units":"μg/mL·h","location":"Results Section 3.8 (p.18)","quote":"AUC(0–t) and AUC(0–∞) values of 326.850 ± 34.180 μg/mL⋅h and 430.550 ± 65.160 μg/mL⋅h","quoteCheck":"supported","note":"Text unit μg/mL·h; Table 11 prints g/L·h"},{"pmid":"42956604","species":"rodent","arm":"","form":"silymarin powder","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"Tmax","detail":"","value":"1.13","variance":"± 0.48 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 gives mean ± SD; letters a/b/c mark significant differences (P<0.05)"},{"pmid":"42956604","species":"rodent","arm":"","form":"silymarin powder","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"Cmax","detail":"","value":"8.46","variance":"± 3.07 (SD)","units":"ng/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42956604","species":"rodent","arm":"","form":"silymarin powder","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"34.23","variance":"± 10.94 (SD)","units":"ng/h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42956604","species":"rodent","arm":"","form":"silymarin powder","forms":["silymarin"],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"AUC","detail":"AUC0-inf","value":"37.86","variance":"± 15.25 (SD)","units":"ng/h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42956604","species":"rodent","arm":"","form":"silymarin liposome (spray-dried) (self-prepared)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"Tmax","detail":"","value":"0.5","variance":"± 0 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42956604","species":"rodent","arm":"","form":"silymarin liposome (spray-dried) (self-prepared)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"Cmax","detail":"","value":"1774.60","variance":"± 980.51 (SD)","units":"ng/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42956604","species":"rodent","arm":"","form":"silymarin liposome (spray-dried) (self-prepared)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"3911.01","variance":"± 3704.44 (SD)","units":"ng/h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42956604","species":"rodent","arm":"","form":"silymarin liposome (spray-dried) (self-prepared)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"AUC","detail":"AUC0-inf","value":"4009.61","variance":"± 3655.05 (SD)","units":"ng/h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42956604","species":"rodent","arm":"","form":"SLM:sunflower phospholipid:Tween 80:sodium alginate microcapsules (self-prepared)","forms":[],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"Tmax","detail":"","value":"0.5","variance":"± 0 (SD)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42956604","species":"rodent","arm":"","form":"SLM:sunflower phospholipid:Tween 80:sodium alginate microcapsules (self-prepared)","forms":[],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"Cmax","detail":"","value":"3926.54","variance":"± 852.89 (SD)","units":"ng/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42956604","species":"rodent","arm":"","form":"SLM:sunflower phospholipid:Tween 80:sodium alginate microcapsules (self-prepared)","forms":[],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"AUC","detail":"AUC0-t","value":"4882.03","variance":"± 2103.18 (SD)","units":"ng/h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42956604","species":"rodent","arm":"","form":"SLM:sunflower phospholipid:Tween 80:sodium alginate microcapsules (self-prepared)","forms":[],"dose":"20 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"AUC","detail":"AUC0-inf","value":"4897.07","variance":"± 2116.86 (SD)","units":"ng/h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"42956604","species":"rodent","arm":"","form":"SLM-NMP redispersion i.v. (self-prepared)","forms":[],"dose":"2 mg/kg","doseBasis":"NR","fed":"fasted 12 h","n":"6","analyte":"silymarin (SLM)","matrix":"serum","parameter":"AUC","detail":"AUC after i.v. SLM-NMP 2 mg/kg (type of AUC interval NR)","value":"1423.14","variance":"± 568.89 (SD)","units":"ng/h/ml","location":"Table 2 footnote","quote":"AUC of SLM-NMP silymarin after i.v. administration of 2 mg/kg body weight was 1423.14 ± 568.89 ng/h/ml","quoteCheck":"supported","note":"n for IV group NR in footnote (groups said n=6); AUC interval (0-t or 0-inf) not stated"},{"pmid":"9008269","species":"rodent","arm":"","form":"aspirin (ASA); sham rats given 0.5% CMC vehicle","forms":[],"dose":"20 mg/kg (aspirin, single oral intragastric dose)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"total salicylates (measured after oral aspirin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"135·0","variance":"± 8·0 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"verified on page image (manager QA)"},{"pmid":"9008269","species":"rodent","arm":"","form":"aspirin (ASA); sham rats given 0.5% CMC vehicle","forms":[],"dose":"20 mg/kg (aspirin, single oral intragastric dose)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"total salicylates (measured after oral aspirin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"20·0","variance":"","units":"min","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Printed without variance; verified on page image (manager QA)"},{"pmid":"9008269","species":"rodent","arm":"","form":"aspirin (ASA); sham rats given 0.5% CMC vehicle","forms":[],"dose":"20 mg/kg (aspirin, single oral intragastric dose)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"total salicylates (measured after oral aspirin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf (trapezoidal with extrapolation to infinity)","value":"183·3","variance":"± 10·0 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"verified on page image (manager QA)"},{"pmid":"9008269","species":"rodent","arm":"","form":"aspirin (ASA)","forms":[],"dose":"20 mg/kg (aspirin, single oral intragastric dose)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"total salicylates (measured after oral aspirin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"152·0","variance":"± 10·0 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"verified on page image (manager QA)"},{"pmid":"9008269","species":"rodent","arm":"","form":"aspirin (ASA)","forms":[],"dose":"20 mg/kg (aspirin, single oral intragastric dose)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"total salicylates (measured after oral aspirin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"30·0","variance":"","units":"min","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Printed without variance; verified on page image (manager QA)"},{"pmid":"9008269","species":"rodent","arm":"","form":"aspirin (ASA)","forms":[],"dose":"20 mg/kg (aspirin, single oral intragastric dose)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"total salicylates (measured after oral aspirin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf (trapezoidal with extrapolation to infinity)","value":"262·0","variance":"± 11·0 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"verified on page image (manager QA)"},{"pmid":"9008269","species":"rodent","arm":"","form":"aspirin (ASA) after silymarin 150 mg/kg p.o. in 0.5% CMC daily x 7 d, started 10 d after surgery","forms":["silymarin"],"dose":"20 mg/kg (aspirin, single oral intragastric dose)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"total salicylates (measured after oral aspirin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"150·0","variance":"± 9·0 (SD)","units":"µg/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"verified on page image (manager QA)"},{"pmid":"9008269","species":"rodent","arm":"","form":"aspirin (ASA) after silymarin 150 mg/kg p.o. in 0.5% CMC daily x 7 d, started 10 d after surgery","forms":["silymarin"],"dose":"20 mg/kg (aspirin, single oral intragastric dose)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"total salicylates (measured after oral aspirin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"20·0","variance":"","units":"min","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Printed without variance; 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verified on page image (manager QA)"},{"pmid":"9008269","species":"rodent","arm":"","form":"aspirin (ASA) after silymarin 150 mg/kg p.o. in 0.5% CMC daily x 7 d","forms":["silymarin"],"dose":"20 mg/kg (aspirin, single oral intragastric dose)","doseBasis":"active compound","fed":"NR","n":"5","analyte":"total salicylates (measured after oral aspirin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf (trapezoidal with extrapolation to infinity)","value":"174·6","variance":"± 12·0 (SD)","units":"µg·h/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"verified on page image (manager QA)"},{"pmid":"16527467","species":"other_animal","arm":"","form":"SMEDDS: silymarin 55.5 (silybin equivalent 22.7), ethyl alcohol 59.4, Tween 80 356.4, ethyl linoleate 178.2 (relative composition, Table 1)","forms":["enhanced"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"Tmax","detail":"rabbit 1","value":"4","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"SMEDDS: silymarin 55.5 (silybin equivalent 22.7), ethyl alcohol 59.4, Tween 80 356.4, ethyl linoleate 178.2 (relative composition, Table 1)","forms":["enhanced"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; 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representing silymarin)","matrix":"plasma","parameter":"Tmax","detail":"rabbit 4","value":"5","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"Cmax","detail":"rabbit 4","value":"0.82","variance":"","units":"µg/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-16h, rabbit 4","value":"4.34","variance":"","units":"µg h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf, rabbit 4","value":"4.90","variance":"","units":"µg h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"Tmax","detail":"rabbit 5","value":"2","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"Cmax","detail":"rabbit 5","value":"0.61","variance":"","units":"µg/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-16h, rabbit 5","value":"1.97","variance":"","units":"µg h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf, rabbit 5","value":"2.32","variance":"","units":"µg h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"Tmax","detail":"rabbit 6","value":"3","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"Cmax","detail":"rabbit 6","value":"0.75","variance":"","units":"µg/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-16h, rabbit 6","value":"2.19","variance":"","units":"µg h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf, rabbit 6","value":"2.33","variance":"","units":"µg h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.39","variance":"± 1.54 (SD)","units":"h","location":"Table 3 (Mean ± SD) / Results 3.4","quote":"","quoteCheck":"no quote","note":"Text order would assign 2.39 ± 1.54 to SMEDDS; table label PEG 400 solution used."},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.70","variance":"± 0.18 (SD)","units":"µg/ml","location":"Table 3 (Mean ± SD) / Results 3.4","quote":"","quoteCheck":"no quote","note":"Text prints 0.71 ± 0.18; Table 3 prints 0.70 ± 0.18. Text lists this value as SMEDDS (order 'solution and SMEDDS'), opposite to table labels."},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-16h","value":"2.85","variance":"± 1.46 (SD)","units":"µg h/ml","location":"Table 3 (Mean ± SD) / Results 3.4","quote":"","quoteCheck":"no quote","note":"Text order would assign 2.85 to SMEDDS; table label PEG 400 solution used."},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin dissolved in PEG 400/dimethylformamide (20/1 v/v)","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"3.17","variance":"± 1.63 (SD)","units":"µg h/ml","location":"Table 3 (Mean ± SD) / Results 3.4","quote":"","quoteCheck":"no quote","note":"Text layer prints 'AUC0-1'; page image shows AUC0-inf."},{"pmid":"16527467","species":"other_animal","arm":"","form":"silymarin milled with 2.5% (v/v) hydroxymethylcellulose solution","forms":["silymarin"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-16h","value":"0.11","variance":"","units":"µg h/ml","location":"Results 3.4","quote":"with AUC0–16h of only 0.11 lg h/ml","quoteCheck":"supported","note":"'Preliminary evaluation of silymarin suspension in six rabbits'; plasma silybin mostly below LOD after 4 h."},{"pmid":"16527467","species":"other_animal","arm":"","form":"SMEDDS: silymarin 55.5 (silybin equivalent 22.7), ethyl alcohol 59.4, Tween 80 356.4, ethyl linoleate 178.2 (relative composition, Table 1)","forms":["enhanced"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability of SMEDDS vs PEG 400 solution, based on AUC0-16h","value":"1.88","variance":"","units":"fold","location":"Abstract / Results 3.4","quote":"mean relative bioavailability of silymarin SMEDDS was 1.88- and 48.82-fold that of silymarin PEG 400 solution and suspension","quoteCheck":"supported","note":"Text says 'average'/'mean'; computed on AUC0-16h per Results 3.4."},{"pmid":"16527467","species":"other_animal","arm":"","form":"SMEDDS: silymarin 55.5 (silybin equivalent 22.7), ethyl alcohol 59.4, Tween 80 356.4, ethyl linoleate 178.2 (relative composition, Table 1)","forms":["enhanced"],"dose":"300 mg/kg (expressed as silybin equivalents)","doseBasis":"active compound","fed":"fasted 12 h","n":"6","analyte":"silybin (total isomers; representing silymarin)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability of SMEDDS vs suspension, based on AUC0-16h","value":"48.82","variance":"","units":"fold","location":"Abstract / Results 3.4","quote":"1.88- and 48.82-fold that of silymarin PEG 400 solution and suspension","quoteCheck":"supported","note":"Suspension arm in separate preliminary evaluation."},{"pmid":"16687221","species":"other_animal","arm":"","form":"20 ml liposome suspension reconstituted from proliposome powder (silymarin 9.73% w/w based on silybin; mannitol carrier; phospholipids), equivalent to 7.7 mg/kg silybin","forms":["enhanced"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"± 0.21 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16687221","species":"other_animal","arm":"","form":"capsule filled with silymarin (30% silybin w/w) equivalent to 7.7 mg/kg silybin","forms":["silymarin"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.5","variance":"± 0.28 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16687221","species":"other_animal","arm":"","form":"20 ml liposome suspension reconstituted from proliposome powder (silymarin 9.73% w/w based on silybin; mannitol carrier; phospholipids), equivalent to 7.7 mg/kg silybin","forms":["enhanced"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"472.62","variance":"± 126.91 (NR)","units":"ng ml-1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Text (Results 3.7) gives average Cmax 472.62 (proliposome) and 89.78 (silymarin) ng ml-1, Tmax about 30 min."},{"pmid":"16687221","species":"other_animal","arm":"","form":"capsule filled with silymarin (30% silybin w/w) equivalent to 7.7 mg/kg silybin","forms":["silymarin"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"89.78","variance":"± 46.07 (NR)","units":"ng ml-1","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16687221","species":"other_animal","arm":"","form":"20 ml liposome suspension reconstituted from proliposome powder (silymarin 9.73% w/w based on silybin; mannitol carrier; phospholipids), equivalent to 7.7 mg/kg silybin","forms":["enhanced"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC (model-based; interval not stated)","value":"2464.62","variance":"± 579.35 (NR)","units":"ng ml-1 h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Abstract prints AUC0-inf 2606.21 (proliposome) and 697 (silymarin); Table 3 prints T(0-inf) 2606.21 and 697.04; Table 2 AUC differs (2464.62 / 717.73)."},{"pmid":"16687221","species":"other_animal","arm":"","form":"capsule filled with silymarin (30% silybin w/w) equivalent to 7.7 mg/kg silybin","forms":["silymarin"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC (model-based; interval not stated)","value":"717.73","variance":"± 156.93 (NR)","units":"ng ml-1 h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Abstract prints AUC0-inf 2606.21 (proliposome) and 697 (silymarin); Table 3 prints T(0-inf) 2606.21 and 697.04; Table 2 AUC differs (2464.62 / 717.73)."},{"pmid":"16687221","species":"other_animal","arm":"","form":"20 ml liposome suspension reconstituted from proliposome powder (silymarin 9.73% w/w based on silybin; mannitol carrier; phospholipids), equivalent to 7.7 mg/kg silybin","forms":["enhanced"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC(s0) T(0-12 h) non-model","value":"1519.81","variance":"± 248.92 (NR)","units":"ng ml-1 h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16687221","species":"other_animal","arm":"","form":"20 ml liposome suspension reconstituted from proliposome powder (silymarin 9.73% w/w based on silybin; mannitol carrier; phospholipids), equivalent to 7.7 mg/kg silybin","forms":["enhanced"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC(s0) T(0-inf) non-model","value":"2606.21","variance":"± 369.42 (NR)","units":"ng ml-1 h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16687221","species":"other_animal","arm":"","form":"capsule filled with silymarin (30% silybin w/w) equivalent to 7.7 mg/kg silybin","forms":["silymarin"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC(s0) T(0-inf) non-model","value":"697.04","variance":"± 286.29 (NR)","units":"ng ml-1 h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"16687221","species":"other_animal","arm":"","form":"capsule filled with silymarin (30% silybin w/w) equivalent to 7.7 mg/kg silybin","forms":["silymarin"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC(s0) T(0-6 h) non-model","value":"358.84","variance":"± 106.46 (NR)","units":"ng ml-1 h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Silymarin control interval is 0-6 h (proliposome 0-12 h), as printed."},{"pmid":"16687221","species":"other_animal","arm":"","form":"20 ml liposome suspension reconstituted from proliposome powder (silymarin 9.73% w/w based on silybin; mannitol carrier; phospholipids), equivalent to 7.7 mg/kg silybin","forms":["enhanced"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"Cmax","detail":"Cmax (text)","value":"472.62","variance":"","units":"ng ml-1","location":"Abstract / Results 3.7","quote":"average value of Cmax was 472.62 ng ml-1 after oral administration of liposomal suspensions","quoteCheck":"supported","note":"Same as Table 2."},{"pmid":"16687221","species":"other_animal","arm":"","form":"capsule filled with silymarin (30% silybin w/w) equivalent to 7.7 mg/kg silybin","forms":["silymarin"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"Cmax","detail":"Cmax (text)","value":"89.78","variance":"","units":"ng ml-1","location":"Abstract / Results 3.7","quote":"average value of Cmax was 89.78 ng ml-1 after oral administration of the capsule full of silymarin","quoteCheck":"supported","note":"Same as Table 2."},{"pmid":"16687221","species":"other_animal","arm":"","form":"20 ml liposome suspension reconstituted from proliposome powder (silymarin 9.73% w/w based on silybin; mannitol carrier; phospholipids), equivalent to 7.7 mg/kg silybin","forms":["enhanced"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"Tmax","detail":"Tmax (text)","value":"30","variance":"","units":"min","location":"Abstract / Results 3.7","quote":"Tmax both 30 min","quoteCheck":"supported","note":"Abstract: 'Tmax both 30 min'."},{"pmid":"16687221","species":"other_animal","arm":"","form":"capsule filled with silymarin (30% silybin w/w) equivalent to 7.7 mg/kg silybin","forms":["silymarin"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"Tmax","detail":"Tmax (text)","value":"30","variance":"","units":"min","location":"Abstract / Results 3.7","quote":"Tmax both 30 min","quoteCheck":"supported","note":""},{"pmid":"16687221","species":"other_animal","arm":"","form":"20 ml liposome suspension reconstituted from proliposome powder (silymarin 9.73% w/w based on silybin; mannitol carrier; phospholipids), equivalent to 7.7 mg/kg silybin","forms":["enhanced"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf (abstract)","value":"2606.21","variance":"","units":"ng mL-1 h","location":"Abstract","quote":"AUC0-∞ 2606.21 and 697 ng mL-1 h, respectively","quoteCheck":"supported","note":"Table 3 prints 2606.21 ± 369.42 (T 0-inf); Table 2 AUC 2464.62."},{"pmid":"16687221","species":"other_animal","arm":"","form":"capsule filled with silymarin (30% silybin w/w) equivalent to 7.7 mg/kg silybin","forms":["silymarin"],"dose":"7.7 mg/kg (as silybin)","doseBasis":"active compound","fed":"fasted 24 h (food withheld 24 h before and after dosing; water allowed)","n":"6","analyte":"silymarin (based on silybin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf (abstract)","value":"697","variance":"","units":"ng mL-1 h","location":"Abstract","quote":"AUC0-∞ 2606.21 and 697 ng mL-1 h, respectively","quoteCheck":"supported","note":"Table 3 prints 697.04 ± 286.29 (T 0-inf); Table 2 AUC 717.73."},{"pmid":"17348898","species":"other_animal","arm":"","form":"Silymarin extract standardized to 80% silymarin (capsule) (Indena USA)","forms":["silymarin"],"dose":"178 mg silybin equivalents (mean 15.74 mg/kg, range 14.2-17.6)","doseBasis":"active compound","fed":"2 h fast (day 7)","n":"8","analyte":"total silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"449","variance":"± 402 (SD)","units":"ng/mL","location":"Table 1","quote":"Cmax (ng/mL) 449 ± 402*","quoteCheck":"supported","note":"Baseline (day -1 and 0 averaged) subtracted"},{"pmid":"17348898","species":"other_animal","arm":"","form":"Silymarin extract standardized to 80% silymarin (capsule) (Indena USA)","forms":["silymarin"],"dose":"178 mg silybin equivalents (mean 15.74 mg/kg, range 14.2-17.6)","doseBasis":"active compound","fed":"23 h fast (day 0)","n":"8","analyte":"total silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"472","variance":"± 383 (SD)","units":"ng/mL","location":"Table 1","quote":"Cmax (ng/mL) 472 ± 383*","quoteCheck":"supported","note":""},{"pmid":"17348898","species":"other_animal","arm":"","form":"Silybin-phosphatidylcholine complex flavored chewable tablet with zinc gluconate and vitamin E (Marin (Nutramax))","forms":["phytosome"],"dose":"178 mg silybin (A + B) equivalents (mean 16.2 mg/kg, range 14.6-17.3)","doseBasis":"active compound","fed":"2 h fast (day 7)","n":"8","analyte":"total silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1310","variance":"± 880 (SD)","units":"ng/mL","location":"Table 1; Abstract","quote":"Cmax (ng/mL) 1310 ± 880*","quoteCheck":"supported","note":""},{"pmid":"17348898","species":"other_animal","arm":"","form":"Silymarin extract standardized to 80% silymarin (capsule) (Indena USA)","forms":["silymarin"],"dose":"178 mg silybin equivalents (mean 15.74 mg/kg, range 14.2-17.6)","doseBasis":"active compound","fed":"2 h fast (day 7)","n":"8","analyte":"total silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"6.87","variance":"± 7.43 (SD)","units":"h","location":"Table 1","quote":"Tmax (h) 6.87 ± 7.43","quoteCheck":"supported","note":""},{"pmid":"17348898","species":"other_animal","arm":"","form":"Silymarin extract standardized to 80% silymarin (capsule) (Indena USA)","forms":["silymarin"],"dose":"178 mg silybin equivalents (mean 15.74 mg/kg, range 14.2-17.6)","doseBasis":"active compound","fed":"23 h fast (day 0)","n":"8","analyte":"total silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"4.75","variance":"± 2.82 (SD)","units":"h","location":"Table 1","quote":"Tmax (h) 4.75 ± 2.82","quoteCheck":"supported","note":""},{"pmid":"17348898","species":"other_animal","arm":"","form":"Silybin-phosphatidylcholine complex flavored chewable tablet with zinc gluconate and vitamin E (Marin (Nutramax))","forms":["phytosome"],"dose":"178 mg silybin (A + B) equivalents (mean 16.2 mg/kg, range 14.6-17.3)","doseBasis":"active compound","fed":"2 h fast (day 7)","n":"8","analyte":"total silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.87","variance":"± 2.23 (SD)","units":"h","location":"Table 1","quote":"Tmax (h) 2.87 ± 2.23","quoteCheck":"supported","note":""},{"pmid":"17348898","species":"other_animal","arm":"","form":"Silymarin extract standardized to 80% silymarin (capsule) (Indena USA)","forms":["silymarin"],"dose":"178 mg silybin equivalents (mean 15.74 mg/kg, range 14.2-17.6)","doseBasis":"active compound","fed":"2 h fast (day 7)","n":"8","analyte":"total silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"2520","variance":"± 2976 (SD)","units":"ng·h/mL","location":"Table 1","quote":"AUC0-24 (ng·h/mL) 2520 ± 2976*","quoteCheck":"supported","note":""},{"pmid":"17348898","species":"other_animal","arm":"","form":"Silymarin extract standardized to 80% silymarin (capsule) (Indena USA)","forms":["silymarin"],"dose":"178 mg silybin equivalents (mean 15.74 mg/kg, range 14.2-17.6)","doseBasis":"active compound","fed":"23 h fast (day 0)","n":"8","analyte":"total silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"3720","variance":"± 4970 (SD)","units":"ng·h/mL","location":"Table 1","quote":"AUC0-24 (ng·h/mL) 3720 ± 4970*","quoteCheck":"supported","note":""},{"pmid":"17348898","species":"other_animal","arm":"","form":"Silybin-phosphatidylcholine complex flavored chewable tablet with zinc gluconate and vitamin E (Marin (Nutramax))","forms":["phytosome"],"dose":"178 mg silybin (A + B) equivalents (mean 16.2 mg/kg, range 14.6-17.3)","doseBasis":"active compound","fed":"2 h fast (day 7)","n":"8","analyte":"total silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"11 200","variance":"± 6520 (SD)","units":"ng·h/mL","location":"Table 1; Abstract","quote":"AUC0-24 (ng·h/mL) 11 200 ± 6520*","quoteCheck":"supported","note":""},{"pmid":"17348898","species":"other_animal","arm":"","form":"Silybin-phosphatidylcholine complex flavored chewable tablet with zinc gluconate and vitamin E (Marin (Nutramax))","forms":["phytosome"],"dose":"178 mg silybin (A + B) equivalents (mean 16.2 mg/kg, range 14.6-17.3)","doseBasis":"active compound","fed":"2 h fast (day 7)","n":"8","analyte":"total silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability of SPC vs extract, first value (3.03) as printed","value":"3.03","variance":"","units":"fold (ratio, as printed 'that of the extract')","location":"Results, Pharmacokinetics (p.134); Discussion p.135","quote":"with a relative bioavailability of 3.03 and 4.44 that of the extract (Table 1)","quoteCheck":"supported","note":"Text does not say which extract group corresponds to 3.03 vs 4.44; Discussion says '3-4.4 fold gain'."},{"pmid":"17348898","species":"other_animal","arm":"","form":"Silybin-phosphatidylcholine complex flavored chewable tablet with zinc gluconate and vitamin E (Marin (Nutramax))","forms":["phytosome"],"dose":"178 mg silybin (A + B) equivalents (mean 16.2 mg/kg, range 14.6-17.3)","doseBasis":"active compound","fed":"2 h fast (day 7)","n":"8","analyte":"total silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability of SPC vs extract, second value (4.44) as printed","value":"4.44","variance":"","units":"fold (ratio, as printed 'that of the extract')","location":"Results, Pharmacokinetics (p.134)","quote":"with a relative bioavailability of 3.03 and 4.44 that of the extract (Table 1)","quoteCheck":"supported","note":"See previous row."},{"pmid":"20405254","species":"other_animal","arm":"","form":"Silymarin self-microemulsifying drug delivery system: ethyl linoleate/Cremophor EL/ethyl alcohol (Experimental)","forms":["silymarin"],"dose":"50 mg/kg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"6","analyte":"silybin (silymarin, measured as total silybin isomers)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.00","variance":"± 0.00 (SD)","units":"h","location":"Table II","quote":"","quoteCheck":"no quote","note":"Tmax: statistic type not stated (mean ± SD per Data Analysis)"},{"pmid":"20405254","species":"other_animal","arm":"","form":"Commercial silymarin hard capsule (Legalon)","forms":["silymarin"],"dose":"50 mg/kg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"6","analyte":"silybin (silymarin, measured as total silybin isomers)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.00","variance":"± 0.00 (SD)","units":"h","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20405254","species":"other_animal","arm":"","form":"Silymarin self-microemulsifying drug delivery system: ethyl linoleate/Cremophor EL/ethyl alcohol (Experimental)","forms":["silymarin"],"dose":"50 mg/kg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"6","analyte":"silybin (silymarin, measured as total silybin isomers)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.85","variance":"± 0.09 (SD)","units":"μg/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20405254","species":"other_animal","arm":"","form":"Commercial silymarin hard capsule (Legalon)","forms":["silymarin"],"dose":"50 mg/kg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"6","analyte":"silybin (silymarin, measured as total silybin isomers)","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.06","variance":"± 0.04 (SD)","units":"μg/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20405254","species":"other_animal","arm":"","form":"Silymarin self-microemulsifying drug delivery system: ethyl linoleate/Cremophor EL/ethyl alcohol (Experimental)","forms":["silymarin"],"dose":"50 mg/kg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"6","analyte":"silybin (silymarin, measured as total silybin isomers)","matrix":"plasma","parameter":"AUC","detail":"AUC0-12h","value":"4.75","variance":"± 0.26 (SD)","units":"μg·h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20405254","species":"other_animal","arm":"","form":"Commercial silymarin hard capsule (Legalon)","forms":["silymarin"],"dose":"50 mg/kg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"6","analyte":"silybin (silymarin, measured as total silybin isomers)","matrix":"plasma","parameter":"AUC","detail":"AUC0-12h","value":"2.09","variance":"± 0.15 (SD)","units":"μg·h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20405254","species":"other_animal","arm":"","form":"Silymarin self-microemulsifying drug delivery system: ethyl linoleate/Cremophor EL/ethyl alcohol (Experimental)","forms":["silymarin"],"dose":"50 mg/kg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"6","analyte":"silybin (silymarin, measured as total silybin isomers)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"5.23","variance":"± 0.21 (SD)","units":"μg·h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20405254","species":"other_animal","arm":"","form":"Commercial silymarin hard capsule (Legalon)","forms":["silymarin"],"dose":"50 mg/kg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"6","analyte":"silybin (silymarin, measured as total silybin isomers)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"2.12","variance":"± 0.07 (SD)","units":"μg·h/mL","location":"Table II","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20405254","species":"other_animal","arm":"","form":"Silymarin self-microemulsifying drug delivery system: ethyl linoleate/Cremophor EL/ethyl alcohol (Experimental)","forms":["silymarin"],"dose":"50 mg/kg silymarin","doseBasis":"salt/compound","fed":"fasted","n":"6","analyte":"silybin (silymarin, measured as total silybin isomers)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability of SMEDDS to Legalon (based on AUC0-12h)","value":"227","variance":"","units":"%","location":"Results p.677; Abstract (about 2.2-fold)","quote":"the relative bioavailability of SMEDDS to Legalon® was 227%","quoteCheck":"supported","note":"Method for calculating not described in Methods; Abstract states about 2.2-fold"},{"pmid":"20523347","species":"other_animal","arm":"","form":"Soluble silybin derivative raw material (Jiangsu Zhongxing)","forms":[],"dose":"90 mg as silybin equivalents","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"118.9","variance":"","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartmental (one-compartment open model, BAPP2.3) parameters; statistic type and variance not stated in table. Table 3 column order is NMG 118.9 and micelles 113.3, but text p.763 states Cmax 118.9 for micelles and 113.3 for NMG (swapped); Table values recorded."},{"pmid":"20523347","species":"other_animal","arm":"","form":"Mixed micelles (silybin 0.2 g, sodium cholate 0.3 g, phospholipid 0.4 g) (Experimental)","forms":["enhanced"],"dose":"90 mg as silybin equivalents","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"113.3","variance":"","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartmental (one-compartment open model, BAPP2.3) parameters; statistic type and variance not stated in table. Table 3 column order is NMG 118.9 and micelles 113.3, but text p.763 states Cmax 118.9 for micelles and 113.3 for NMG (swapped); Table values recorded."},{"pmid":"20523347","species":"other_animal","arm":"","form":"Soluble silybin derivative raw material (Jiangsu Zhongxing)","forms":[],"dose":"90 mg as silybin equivalents","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartmental (one-compartment open model, BAPP2.3) parameters; statistic type and variance not stated in table"},{"pmid":"20523347","species":"other_animal","arm":"","form":"Mixed micelles (silybin 0.2 g, sodium cholate 0.3 g, phospholipid 0.4 g) (Experimental)","forms":["enhanced"],"dose":"90 mg as silybin equivalents","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1","variance":"","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartmental (one-compartment open model, BAPP2.3) parameters; statistic type and variance not stated in table"},{"pmid":"20523347","species":"other_animal","arm":"","form":"Soluble silybin derivative raw material (Jiangsu Zhongxing)","forms":[],"dose":"90 mg as silybin equivalents","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-τ (AUC0-24 per Methods)","value":"439.7","variance":"","units":"h·ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartmental (one-compartment open model, BAPP2.3) parameters; statistic type and variance not stated in table"},{"pmid":"20523347","species":"other_animal","arm":"","form":"Mixed micelles (silybin 0.2 g, sodium cholate 0.3 g, phospholipid 0.4 g) (Experimental)","forms":["enhanced"],"dose":"90 mg as silybin equivalents","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-τ (AUC0-24 per Methods)","value":"1108.0","variance":"","units":"h·ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartmental (one-compartment open model, BAPP2.3) parameters; statistic type and variance not stated in table"},{"pmid":"20523347","species":"other_animal","arm":"","form":"Soluble silybin derivative raw material (Jiangsu Zhongxing)","forms":[],"dose":"90 mg as silybin equivalents","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"505.8","variance":"","units":"h·ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartmental (one-compartment open model, BAPP2.3) parameters; statistic type and variance not stated in table"},{"pmid":"20523347","species":"other_animal","arm":"","form":"Mixed micelles (silybin 0.2 g, sodium cholate 0.3 g, phospholipid 0.4 g) (Experimental)","forms":["enhanced"],"dose":"90 mg as silybin equivalents","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"1372.4","variance":"","units":"h·ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartmental (one-compartment open model, BAPP2.3) parameters; statistic type and variance not stated in table"},{"pmid":"20523347","species":"other_animal","arm":"","form":"Mixed micelles (silybin 0.2 g, sodium cholate 0.3 g, phospholipid 0.4 g) (Experimental)","forms":["enhanced"],"dose":"90 mg as silybin equivalents","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"Cmax as stated in Results text","value":"118.9","variance":"","units":"ng/mL","location":"Results p.763","quote":"The Cmax values were 118.9 and 113.3 ng/mL for silybin-sodium cholate/phospholipid-mixed micelles and silybin-N-methylglucamine","quoteCheck":"supported","note":"Inconsistent with Table 3 (micelles 113.3)"},{"pmid":"20523347","species":"other_animal","arm":"","form":"Soluble silybin derivative raw material (Jiangsu Zhongxing)","forms":[],"dose":"90 mg as silybin equivalents","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"Cmax as stated in Results text","value":"113.3","variance":"","units":"ng/mL","location":"Results p.763","quote":"","quoteCheck":"no quote","note":"Inconsistent with Table 3 (NMG 118.9)"},{"pmid":"20523347","species":"other_animal","arm":"","form":"Mixed micelles (silybin 0.2 g, sodium cholate 0.3 g, phospholipid 0.4 g) (Experimental)","forms":["enhanced"],"dose":"90 mg as silybin equivalents","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr = AUC0-24(micelles)/AUC0-24(NMG)","value":"252.0","variance":"","units":"%","location":"Abstract; Results p.763","quote":"relative bioavailability of mixed micelles versus silybin-N-methylglucamine in dogs was 252.0%","quoteCheck":"supported","note":"Abstract and Discussion: 252.0%; also AUC0-inf stated as approximately 2.7-fold greater in text (1372.4 vs 505.8)"},{"pmid":"20621458","species":"other_animal","arm":"","form":"Nanostructured lipid carriers (GMS/MCT/lecithin), freeze-dried, mean size 232.1 nm (Experimental)","forms":["enhanced"],"dose":"4 mg/kg silybin equivalents","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0–t)","value":"6.267","variance":"","units":"mg L−1 h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Mean; variance not given in table"},{"pmid":"20621458","species":"other_animal","arm":"","form":"Silybin in PEG 400/ethanol/water 4/1/5","forms":[],"dose":"4 mg/kg silybin equivalents","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0–t)","value":"2.979","variance":"","units":"mg L−1 h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Mean; variance not given in table"},{"pmid":"20621458","species":"other_animal","arm":"","form":"Nanostructured lipid carriers (GMS/MCT/lecithin), freeze-dried, mean size 232.1 nm (Experimental)","forms":["enhanced"],"dose":"4 mg/kg silybin equivalents","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0–∞)","value":"6.271","variance":"","units":"mg L−1 h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Mean; variance not given in table"},{"pmid":"20621458","species":"other_animal","arm":"","form":"Silybin in PEG 400/ethanol/water 4/1/5","forms":[],"dose":"4 mg/kg silybin equivalents","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0–∞)","value":"2.981","variance":"","units":"mg L−1 h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Mean; variance not given in table"},{"pmid":"20621458","species":"other_animal","arm":"","form":"Silybin-NLC (Experimental)","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0–t) of tissue/plasma concentration-time curve","value":"28.322","variance":"","units":"mg L−1 h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20621458","species":"other_animal","arm":"","form":"Silybin solution","forms":[],"dose":"12 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"4","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0–t) of tissue/plasma concentration-time curve","value":"18.006","variance":"","units":"mg L−1 h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21666703","species":"other_animal","arm":"","form":"dehydrosilymarin powder suspended in water (milled)","forms":["silymarin"],"dose":"80 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"dehydrosilybin (dehydrosilymarin main active)","matrix":"plasma","parameter":"AUC","detail":"AUCt (to 12 h)","value":"5.58","variance":"± 0.21 (SD)","units":"μg·mL–1·h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21666703","species":"other_animal","arm":"","form":"proliposomes (soybean phospholipid, cholesterol, isopropyl myristate, sodium cholate) dispersed in water","forms":["enhanced"],"dose":"80 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"dehydrosilybin (dehydrosilymarin main active)","matrix":"plasma","parameter":"AUC","detail":"AUCt (to 12 h)","value":"12.77","variance":"± 1.39 (SD)","units":"μg·mL–1·h","location":"Table 2","quote":"","quoteCheck":"no quote","note":""},{"pmid":"21666703","species":"other_animal","arm":"","form":"dehydrosilymarin powder suspended in water (milled)","forms":["silymarin"],"dose":"80 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"dehydrosilybin (dehydrosilymarin main active)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.00","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"No variance printed; Table 2 header says data expressed as mean±SD; text also gives tmax 2.00 h and 0.50 h"},{"pmid":"21666703","species":"other_animal","arm":"","form":"proliposomes (soybean phospholipid, cholesterol, isopropyl myristate, sodium cholate) dispersed in water","forms":["enhanced"],"dose":"80 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"dehydrosilybin (dehydrosilymarin main active)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.50","variance":"","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"No variance printed; Table 2 header says data expressed as mean±SD; text also gives tmax 2.00 h and 0.50 h"},{"pmid":"21666703","species":"other_animal","arm":"","form":"dehydrosilymarin powder suspended in water (milled)","forms":["silymarin"],"dose":"80 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"dehydrosilybin (dehydrosilymarin main active)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.57","variance":"","units":"μg/mL","location":"Results p.976-977","quote":"Cmax was approximately 0.57 μg/mL","quoteCheck":"supported","note":"Printed as 'approximately' in text; Cmax not in Table 2; variance NR"},{"pmid":"21666703","species":"other_animal","arm":"","form":"proliposomes (soybean phospholipid, cholesterol, isopropyl myristate, sodium cholate) dispersed in water","forms":["enhanced"],"dose":"80 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"dehydrosilybin (dehydrosilymarin main active)","matrix":"plasma","parameter":"Cmax","detail":"","value":"2.83","variance":"","units":"μg/mL","location":"Results p.976-977","quote":"the value of Cmax was approximately 2.83 μg/mL","quoteCheck":"supported","note":"Printed as 'approximately' in text; Cmax not in Table 2; variance NR"},{"pmid":"21666703","species":"other_animal","arm":"","form":"proliposomes (soybean phospholipid, cholesterol, isopropyl myristate, sodium cholate) dispersed in water","forms":["enhanced"],"dose":"80 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"dehydrosilybin (dehydrosilymarin main active)","matrix":"plasma","parameter":"relative_bioavailability","detail":"AUCt-based, proliposomes vs suspension","value":"228.85","variance":"","units":"%","location":"Abstract; Results p.977","quote":"the relative bioavailability of proliposomes versus suspension in rabbits was 228.85%","quoteCheck":"supported","note":""},{"pmid":"21666703","species":"other_animal","arm":"","form":"dehydrosilymarin powder suspended in water (milled)","forms":["silymarin"],"dose":"80 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"dehydrosilybin (dehydrosilymarin main active)","matrix":"plasma","parameter":"fractional_absorption","detail":"Fa: in vivo absorption percent (Wagner-Nelson, per authors)","value":"41.59","variance":"","units":"%","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Same Fa values printed in Table 3 rows for pH 1.2 and pH 6.8 (used for IVIVC at both pH); recorded once"},{"pmid":"21666703","species":"other_animal","arm":"","form":"proliposomes (soybean phospholipid, cholesterol, isopropyl myristate, sodium cholate) dispersed in water","forms":["enhanced"],"dose":"80 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"dehydrosilybin (dehydrosilymarin main active)","matrix":"plasma","parameter":"fractional_absorption","detail":"Fa: in vivo absorption percent (Wagner-Nelson, per authors)","value":"25.33","variance":"","units":"%","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Same Fa values printed in Table 3 rows for pH 1.2 and pH 6.8 (used for IVIVC at both pH); recorded once"},{"pmid":"21948306","species":"other_animal","arm":"","form":"glyceryl monooleate/poloxamer 407 liquid crystalline matrix with silymarin 4%","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.75","variance":"± 0.92 (NR)","units":"h","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD); significance marks: <0.05 vs gel (**)"},{"pmid":"21948306","species":"other_animal","arm":"","form":"glyceryl monooleate/poloxamer 407 liquid crystalline matrix with silymarin 4%","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"2.27","variance":"± 1.07 (NR)","units":"µg/ml","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD); significance marks: <0.05 vs Legalon and vs gel (*,**)"},{"pmid":"21948306","species":"other_animal","arm":"","form":"glyceryl monooleate/poloxamer 407 liquid crystalline matrix with silymarin 4%","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"5.31","variance":"± 3.59 (NR)","units":"µg×h/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD); significance marks: <0.05 vs Legalon (*)"},{"pmid":"21948306","species":"other_animal","arm":"","form":"glyceryl monooleate/poloxamer 407 liquid crystalline matrix with silymarin 4%","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"5.46","variance":"± 3.57 (NR)","units":"µg×h/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD); significance marks: <0.05 vs Legalon (*)"},{"pmid":"21948306","species":"other_animal","arm":"","form":"silymarin cubic gel (about 2.4% silymarin) sealed in hard gelatin capsules","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"2.55","variance":"± 1.39 (NR)","units":"h","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD); significance marks: <0.05 vs Legalon (*)"},{"pmid":"21948306","species":"other_animal","arm":"","form":"silymarin cubic gel (about 2.4% silymarin) sealed in hard gelatin capsules","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"3.41","variance":"± 2.05 (NR)","units":"µg/ml","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD); significance marks: <0.05 vs Legalon (*)"},{"pmid":"21948306","species":"other_animal","arm":"","form":"silymarin cubic gel (about 2.4% silymarin) sealed in hard gelatin capsules","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"5.65","variance":"± 2.58 (NR)","units":"µg×h/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD); significance marks: <0.05 vs Legalon (*)"},{"pmid":"21948306","species":"other_animal","arm":"","form":"silymarin cubic gel (about 2.4% silymarin) sealed in hard gelatin capsules","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"5.78","variance":"± 2.58 (NR)","units":"µg×h/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD); significance marks: <0.05 vs Legalon (*)"},{"pmid":"21948306","species":"other_animal","arm":"","form":"commercial silymarin capsule (Legalon)","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.70","variance":"± 0.67 (NR)","units":"h","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD)"},{"pmid":"21948306","species":"other_animal","arm":"","form":"commercial silymarin capsule (Legalon)","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.76","variance":"± 0.36 (NR)","units":"µg/ml","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD)"},{"pmid":"21948306","species":"other_animal","arm":"","form":"commercial silymarin capsule (Legalon)","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"1.54","variance":"± 0.57 (NR)","units":"µg×h/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD)"},{"pmid":"21948306","species":"other_animal","arm":"","form":"commercial silymarin capsule (Legalon)","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"4.023","variance":"± 2.13 (NR)","units":"µg×h/mL","location":"Table I","quote":"","quoteCheck":"no quote","note":"Table I prints value ± value without naming variance type (Fig. 7 caption states mean±SD); AUC0-inf (4.023) is larger than AUC0-t (1.54) as printed"},{"pmid":"21948306","species":"other_animal","arm":"","form":"glyceryl monooleate/poloxamer 407 liquid crystalline matrix with silymarin 4%","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"relative_bioavailability","detail":"based on AUC0-t, Legalon as reference","value":"345.57","variance":"","units":"%","location":"Table I; Results p.1239","quote":"The relative bioavailability of GMO/P407 LCM and liquid crystalline gel was 345.57% and 367.9%, respectively, with Legalon as the reference","quoteCheck":"supported","note":"Table I footnote a: calculated on AUC0-t; Abstract states 3.46-fold, Conclusion states 3.5-fold"},{"pmid":"21948306","species":"other_animal","arm":"","form":"silymarin cubic gel (about 2.4% silymarin) sealed in hard gelatin capsules","forms":["silymarin"],"dose":"14.4 mg/kg","doseBasis":"active compound","fed":"fasted 24 h","n":"6","analyte":"silybin (main component of silymarin)","matrix":"plasma","parameter":"relative_bioavailability","detail":"based on AUC0-t, Legalon as reference","value":"367.90","variance":"","units":"%","location":"Table I; Results p.1239","quote":"","quoteCheck":"no quote","note":"Table I footnote a: calculated on AUC0-t; text prints 367.9%"},{"pmid":"24495272","species":"other_animal","arm":"","form":"oral aqueous suspension (0.5% silybin, 0.1% SDS, high-pressure homogenization)","forms":[],"dose":"200 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"T(peak)","value":"0.96","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"oral aqueous suspension (0.5% silybin, 0.1% SDS, high-pressure homogenization)","forms":[],"dose":"200 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"C(max)","value":"326.52","variance":"","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"oral aqueous suspension (0.5% silybin, 0.1% SDS, high-pressure homogenization)","forms":[],"dose":"200 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"3744.35","variance":"","units":"(ng/mL) × h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"oral suspension","forms":[],"dose":"200 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"T(peak)","value":"0.90","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"oral suspension","forms":[],"dose":"200 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"C(max)","value":"237.42","variance":"","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"oral suspension","forms":[],"dose":"200 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"2771.66","variance":"","units":"(ng/mL) × h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"oral suspension of coarse silybin","forms":[],"dose":"200 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"T(peak)","value":"0.93","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"oral suspension of coarse silybin","forms":[],"dose":"200 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"C(max)","value":"130.55","variance":"","units":"ng/mL","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"oral suspension of coarse silybin","forms":[],"dose":"200 mg/kg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"763.13","variance":"","units":"(ng/mL) × h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"tablet from spray-dried silybin nanocrystals (SDS, mannitol), 250 mg tablet","forms":["enhanced"],"dose":"50 mg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"T(peak)","value":"0.60","variance":"","units":"H","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed; unit printed as capital H"},{"pmid":"24495272","species":"other_animal","arm":"","form":"tablet from spray-dried silybin nanocrystals (SDS, mannitol), 250 mg tablet","forms":["enhanced"],"dose":"50 mg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"C(max)","value":"241.43","variance":"","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"tablet from spray-dried silybin nanocrystals (SDS, mannitol), 250 mg tablet","forms":["enhanced"],"dose":"50 mg","doseBasis":"active compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"3600.95","variance":"","units":"(ng/mL) × h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"silybin meglumine tablet (water-soluble salt) (commercially available (brand NR))","forms":["enhanced"],"dose":"50 mg","doseBasis":"salt/compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"T(peak)","value":"0.53","variance":"","units":"H","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed; unit printed as capital H"},{"pmid":"24495272","species":"other_animal","arm":"","form":"silybin meglumine tablet (water-soluble salt) (commercially available (brand NR))","forms":["enhanced"],"dose":"50 mg","doseBasis":"salt/compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"C(max)","value":"133.81","variance":"","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"silybin meglumine tablet (water-soluble salt) (commercially available (brand NR))","forms":["enhanced"],"dose":"50 mg","doseBasis":"salt/compound","fed":"NR","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"2621.55","variance":"","units":"(ng/mL) × h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Compartment model parameter; no variance printed"},{"pmid":"24495272","species":"other_animal","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"nanocrystal tablet (T) vs silybin meglumine tablet (R), dose-adjusted (as stated)","value":"97.8","variance":"","units":"%","location":"Results p.557","quote":"no significant difference in absorption rate and extent ... both with a relative bioavailability of 97.8%","quoteCheck":"supported","note":"Text says 'both with a relative bioavailability of 97.8%'; calculation basis (dose adjustment) not shown; sentence as printed."},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin-loaded NLCs (Precirol ATO 5 + oleic acid + lecithin)","forms":["silymarin"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.27","variance":"± 0.38 (NR)","units":"µg/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin-loaded NLCs (Precirol ATO 5 + oleic acid + lecithin)","forms":["silymarin"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.63","variance":"± 0.31 (NR)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin-loaded NLCs (Precirol ATO 5 + oleic acid + lecithin)","forms":["silymarin"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8 (h µg/ml)","value":"1.75","variance":"± 0.47 (NR)","units":"h µg/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables; table header AUC0-8, text calls it AUC0-t"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin-loaded NLCs (Precirol ATO 5 + oleic acid + lecithin)","forms":["silymarin"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"vs integral NLC taken as 100%","value":"100","variance":"","units":"%","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Reference arm, printed as 100"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-NLCs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.83","variance":"± 0.33 (NR)","units":"µg/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables; asterisk = P < 0.05 vs reference"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-NLCs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.38","variance":"± 0.21 (NR)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-NLCs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8 (h µg/ml)","value":"1.31","variance":"± 0.49 (NR)","units":"h µg/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables; table header AUC0-8, text calls it AUC0-t"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-NLCs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"vs integral NLC taken as 100%","value":"74.86","variance":"","units":"%","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Reference arm printed as 100; asterisk = P < 0.05 vs reference"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin/PVP solid dispersion powder (SMSD) mixed with blank NLCs","forms":["enhanced"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.00","variance":"± 0.42 (NR)","units":"µg/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin/PVP solid dispersion powder (SMSD) mixed with blank NLCs","forms":["enhanced"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.63","variance":"± 0.26 (NR)","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin/PVP solid dispersion powder (SMSD) mixed with blank NLCs","forms":["enhanced"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8 (h µg/ml)","value":"1.15","variance":"± 0.53 (NR)","units":"h µg/ml","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables; asterisk = P < 0.05 vs reference; table header AUC0-8, text calls it AUC0-t"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin/PVP solid dispersion powder (SMSD) mixed with blank NLCs","forms":["enhanced"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"vs integral NLC taken as 100%","value":"65.71","variance":"","units":"%","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Reference arm printed as 100; asterisk = P < 0.05 vs reference"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin-loaded SLNs (Precirol ATO 5, no oleic acid)","forms":["silymarin"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.28","variance":"± 0.42 (NR)","units":"µg/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin-loaded SLNs (Precirol ATO 5, no oleic acid)","forms":["silymarin"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.75","variance":"± 0.22 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin-loaded SLNs (Precirol ATO 5, no oleic acid)","forms":["silymarin"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8 (h µg/ml)","value":"2.22","variance":"± 0.76 (NR)","units":"h µg/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables; table header AUC0-8, text calls it AUC0-t"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin-loaded SLNs (Precirol ATO 5, no oleic acid)","forms":["silymarin"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"vs integral SLN taken as 100%","value":"100","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Reference arm, printed as 100"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-SLNs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.80","variance":"± 0.29 (NR)","units":"µg/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables; asterisk = P < 0.05 vs reference"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-SLNs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.58","variance":"± 0.26 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-SLNs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8 (h µg/ml)","value":"1.30","variance":"± 0.34 (NR)","units":"h µg/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables; asterisk = P < 0.05 vs reference; table header AUC0-8, text calls it AUC0-t"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-SLNs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"vs integral SLN taken as 100%","value":"58.56","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Reference arm printed as 100; asterisk = P < 0.05 vs reference"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin/PVP solid dispersion powder (SMSD) mixed with blank SLNs","forms":["enhanced"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.82","variance":"± 0.33 (NR)","units":"µg/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables; asterisk = P < 0.05 vs reference"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin/PVP solid dispersion powder (SMSD) mixed with blank SLNs","forms":["enhanced"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.50","variance":"± 0.21 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin/PVP solid dispersion powder (SMSD) mixed with blank SLNs","forms":["enhanced"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-8 (h µg/ml)","value":"0.89","variance":"± 0.21 (NR)","units":"h µg/ml","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 1/2 print mean ± value without naming the variance type (Fig. 6/7 captions state mean ± SD); statistic type not named in tables; asterisk = P < 0.05 vs reference; table header AUC0-8, text calls it AUC0-t"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin/PVP solid dispersion powder (SMSD) mixed with blank SLNs","forms":["enhanced"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"vs integral SLN taken as 100%","value":"40.09","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Reference arm printed as 100; asterisk = P < 0.05 vs reference"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin-loaded SLNs (Precirol ATO 5, no oleic acid)","forms":["silymarin"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative to SM-NLC taken as 100%","value":"126.9","variance":"","units":"%","location":"Results 3.4 (p. 200)","quote":"Taking the bioavailability of NLCs as 100%, the calculated relative bioavailability of NLC lipolysates and the SD mixture was 74.86% and 65.71%, while those for SLNs, SLN lipolysates and the SD mixture were 126.9%, 74.29% and 50.86%","quoteCheck":"supported","note":"Text; NLC taken as the 100% reference across both series (differs from Table 2 where SLN is 100%)"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-SLNs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative to SM-NLC taken as 100%","value":"74.29","variance":"","units":"%","location":"Results 3.4 (p. 200)","quote":"Taking the bioavailability of NLCs as 100%, the calculated relative bioavailability of NLC lipolysates and the SD mixture was 74.86% and 65.71%, while those for SLNs, SLN lipolysates and the SD mixture were 126.9%, 74.29% and 50.86%","quoteCheck":"supported","note":"Differs from Table 2 value 58.56 (reference there is SM-SLN); different reference arm in text"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin/PVP solid dispersion powder (SMSD) mixed with blank SLNs","forms":["enhanced"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative to SM-NLC taken as 100%","value":"50.86","variance":"","units":"%","location":"Results 3.4 (p. 200)","quote":"Taking the bioavailability of NLCs as 100%, the calculated relative bioavailability of NLC lipolysates and the SD mixture was 74.86% and 65.71%, while those for SLNs, SLN lipolysates and the SD mixture were 126.9%, 74.29% and 50.86%","quoteCheck":"supported","note":"Differs from Table 2 value 40.09 (reference there is SM-SLN); different reference arm in text"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-NLCs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"decrease vs integral NLC as printed in Abstract","value":"74.86%","variance":"","units":"%","location":"Abstract","quote":"Pharmacokinetics analysis in dogs showed a decrease in bioavailability of 74.86% and 59.09% for lipolysates compared to integral NLCs and SLNs, respectively.","quoteCheck":"supported","note":"Abstract words it as a 'decrease of 74.86%' but 74.86% is the relative bioavailability in Table 1 (inconsistent wording)"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-SLNs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"decrease vs integral SLN as printed in Abstract","value":"59.09%","variance":"","units":"%","location":"Abstract","quote":"a decrease in bioavailability of 74.86% and 59.09% for lipolysates compared to integral NLCs and SLNs, respectively","quoteCheck":"supported","note":"Abstract value 59.09% differs from Table 2 value 58.56%; Conclusion says approximately 60%"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-SLNs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability approx. as printed in Conclusion","value":"approximately 60%","variance":"","units":"%","location":"Conclusion (p. 201)","quote":"the bioavailability of lipolysates of NLCs and SLNs being approximately 75% and 60%, respectively","quoteCheck":"value not in quote","note":"Approximate value printed in Conclusion; arm = SLN lipolysate"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-NLCs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability approx. as printed in Conclusion","value":"approximately 75%","variance":"","units":"%","location":"Conclusion (p. 201)","quote":"the bioavailability of lipolysates of NLCs and SLNs being approximately 75% and 60%, respectively","quoteCheck":"supported","note":"Approximate value printed in Conclusion"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-SLNs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t (as named in text)","value":"1.30","variance":"","units":"h µg/mL","location":"Results 3.4 (p. 200)","quote":"1.30 and 1.31 h µg/mL for SLN and NLC lipolysates, respectively (P>0.05)... 2.22 vs. 1.75 h µg/mL","quoteCheck":"supported","note":"Same value as Table 2 AUC0-8; text labels it AUC0-t"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Lipolysate of SM-NLCs produced by in vitro lipolysis in FeSSIF","forms":[],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t (as named in text)","value":"1.31","variance":"","units":"h µg/mL","location":"Results 3.4 (p. 200)","quote":"1.30 and 1.31 h µg/mL for SLN and NLC lipolysates, respectively (P>0.05)... 2.22 vs. 1.75 h µg/mL","quoteCheck":"supported","note":"Same value as Table 1 AUC0-8; text labels it AUC0-t"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin-loaded SLNs (Precirol ATO 5, no oleic acid)","forms":["silymarin"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t (as named in text)","value":"2.22","variance":"","units":"h µg/mL","location":"Results 3.4 (p. 200)","quote":"1.30 and 1.31 h µg/mL for SLN and NLC lipolysates, respectively (P>0.05)... 2.22 vs. 1.75 h µg/mL","quoteCheck":"supported","note":"Same value as Table 2 AUC0-8; text labels it AUC0-t"},{"pmid":"25956049","species":"other_animal","arm":"","form":"Silymarin-loaded NLCs (Precirol ATO 5 + oleic acid + lecithin)","forms":["silymarin"],"dose":"8 mg/kg","doseBasis":"active compound","fed":"fasted 12 h (dogs)","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t (as named in text)","value":"1.75","variance":"","units":"h µg/mL","location":"Results 3.4 (p. 200)","quote":"1.30 and 1.31 h µg/mL for SLN and NLC lipolysates, respectively (P>0.05)... 2.22 vs. 1.75 h µg/mL","quoteCheck":"supported","note":"Same value as Table 1 AUC0-8; text labels it AUC0-t"},{"pmid":"25956049","species":"other_animal","arm":"","form":"","forms":[],"dose":"","doseBasis":"","fed":"","n":"","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"SMSD (solid dispersion pellets alone, from previous study) vs NLCs taken as reference","value":"32.22%","variance":"","units":"%","location":"Results 3.4 (p. 200)","quote":"NLCs > NLCs lipolysates (74.86%) > SMSD–NLCs mixture (65.71%) > SMSD (32.22%)","quoteCheck":"supported","note":"SMSD alone was not an arm in this study; value comes from previous study (Shangguan et al., 2014) as cited in text"},{"pmid":"26669888","species":"other_animal","arm":"","form":"capsule containing silybin-loaded calcium phosphate microparticles (povidone/sodium cholate/phospholipid micelle-templated)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water allowed","n":"4","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"418.5","variance":"± 23.7 (SD)","units":"ng mL⁻¹","location":"Table I; Abstract","quote":"Cmax (418.5±23.7 ng mL−1)","quoteCheck":"supported","note":""},{"pmid":"26669888","species":"other_animal","arm":"","form":"capsule containing silybin-loaded calcium phosphate microparticles (povidone/sodium cholate/phospholipid micelle-templated)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water allowed","n":"4","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"4","variance":"","units":"h","location":"Table I","quote":"","quoteCheck":"no quote","note":"No variance printed; text says 'about 4 h' / 'about 2 h'"},{"pmid":"26669888","species":"other_animal","arm":"","form":"capsule containing silybin-loaded calcium phosphate microparticles (povidone/sodium cholate/phospholipid micelle-templated)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water allowed","n":"4","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-τ","value":"3821.4","variance":"± 267.4 (SD)","units":"ng mL⁻¹ h","location":"Table I","quote":"","quoteCheck":"no quote","note":"τ (end of sampling) not defined in table; sampling to 24 h"},{"pmid":"26669888","species":"other_animal","arm":"","form":"capsule containing silybin-loaded calcium phosphate microparticles (povidone/sodium cholate/phospholipid micelle-templated)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water allowed","n":"4","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"4374.2","variance":"± 344.1 (SD)","units":"ng mL⁻¹ h","location":"Table I","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26669888","species":"other_animal","arm":"","form":"capsule containing free silybin","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water allowed","n":"4","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"112.4","variance":"± 8.4 (SD)","units":"ng mL⁻¹","location":"Table I; Abstract","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26669888","species":"other_animal","arm":"","form":"capsule containing free silybin","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water allowed","n":"4","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"2","variance":"","units":"h","location":"Table I","quote":"","quoteCheck":"no quote","note":"No variance printed; text says 'about 4 h' / 'about 2 h'"},{"pmid":"26669888","species":"other_animal","arm":"","form":"capsule containing free silybin","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water allowed","n":"4","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-τ","value":"1529.0","variance":"± 105.6 (SD)","units":"ng mL⁻¹ h","location":"Table I","quote":"","quoteCheck":"no quote","note":"τ (end of sampling) not defined in table; sampling to 24 h"},{"pmid":"26669888","species":"other_animal","arm":"","form":"capsule containing free silybin","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water allowed","n":"4","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"2611.3","variance":"± 153.6 (SD)","units":"ng mL⁻¹ h","location":"Table I","quote":"","quoteCheck":"no quote","note":""},{"pmid":"26669888","species":"other_animal","arm":"","form":"capsule containing silybin-loaded calcium phosphate microparticles (povidone/sodium cholate/phospholipid micelle-templated)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted 24 h, water allowed","n":"4","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"vs free silybin","value":"167.5%","variance":"","units":"%","location":"Abstract; Results p. 1237","quote":"the relative bioavailability of silybin-loaded calcium phosphate microparticles in contrast with free silybin was about 167.5%","quoteCheck":"supported","note":"Authors' calculation (not shown which AUC); Results says 'about 167.5%'; AUC0-∞ ratio 4374.2/2611.3 would be ~1.675 (not computed by extractor)"},{"pmid":"32654568","species":"other_animal","arm":"","form":"Silymarin plus capsule (Silymarin plus (Sedico))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"585","variance":"± 4.76 (NR)","units":"ng/ml","location":"Table 10","quote":"","quoteCheck":"no quote","note":"mean/SD/SEM not stated; ± as printed"},{"pmid":"32654568","species":"other_animal","arm":"","form":"floating microspheres (HPMC/EC blend, formula F24)","forms":[],"dose":"200 mg (microspheres equivalent to 200 mg silymarin per Methods)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1021.3","variance":"± 7.7 (NR)","units":"ng/ml","location":"Table 10","quote":"","quoteCheck":"no quote","note":"mean/SD/SEM not stated; ± as printed"},{"pmid":"32654568","species":"other_animal","arm":"","form":"Silymarin plus capsule (Silymarin plus (Sedico))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1","variance":"","units":"hr","location":"Table 10","quote":"","quoteCheck":"no quote","note":"no variance printed"},{"pmid":"32654568","species":"other_animal","arm":"","form":"floating microspheres (HPMC/EC blend, formula F24)","forms":[],"dose":"200 mg (microspheres equivalent to 200 mg silymarin per Methods)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"6","variance":"","units":"hr","location":"Table 10","quote":"","quoteCheck":"no quote","note":"no variance printed"},{"pmid":"32654568","species":"other_animal","arm":"","form":"Silymarin plus capsule (Silymarin plus (Sedico))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"4017.5","variance":"± 24.06 (NR)","units":"ng.hr/ml","location":"Table 10","quote":"","quoteCheck":"no quote","note":"mean/SD/SEM not stated; ± as printed"},{"pmid":"32654568","species":"other_animal","arm":"","form":"floating microspheres (HPMC/EC blend, formula F24)","forms":[],"dose":"200 mg (microspheres equivalent to 200 mg silymarin per Methods)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"9119.8","variance":"± 18.23 (NR)","units":"ng.hr/ml","location":"Table 10","quote":"","quoteCheck":"no quote","note":"mean/SD/SEM not stated; ± as printed"},{"pmid":"32654568","species":"other_animal","arm":"","form":"Silymarin plus capsule (Silymarin plus (Sedico))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC24-∞","value":"1.5","variance":"± 0.3507 (NR)","units":"ng.hr/ml","location":"Table 10","quote":"","quoteCheck":"no quote","note":"mean/SD/SEM not stated; ± as printed"},{"pmid":"32654568","species":"other_animal","arm":"","form":"floating microspheres (HPMC/EC blend, formula F24)","forms":[],"dose":"200 mg (microspheres equivalent to 200 mg silymarin per Methods)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC24-∞","value":"1.755","variance":"± 0.39 (NR)","units":"ng.hr/ml","location":"Table 10","quote":"","quoteCheck":"no quote","note":"mean/SD/SEM not stated; ± as printed"},{"pmid":"32654568","species":"other_animal","arm":"","form":"Silymarin plus capsule (Silymarin plus (Sedico))","forms":["silymarin"],"dose":"200 mg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"4019","variance":"± 23.73 (NR)","units":"ng.hr/ml","location":"Table 10","quote":"","quoteCheck":"no quote","note":"mean/SD/SEM not stated; ± as printed"},{"pmid":"32654568","species":"other_animal","arm":"","form":"floating microspheres (HPMC/EC blend, formula F24)","forms":[],"dose":"200 mg (microspheres equivalent to 200 mg silymarin per Methods)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"9119","variance":"± 18.23 (NR)","units":"ng.hr/ml","location":"Table 10","quote":"","quoteCheck":"no quote","note":"mean/SD/SEM not stated; ± as printed"},{"pmid":"32654568","species":"other_animal","arm":"","form":"floating microspheres (HPMC/EC blend, formula F24)","forms":[],"dose":"200 mg (microspheres equivalent to 200 mg silymarin per Methods)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"RB% = AUC0-24 test / AUC0-24 reference","value":"227","variance":"","units":"%","location":"Table 10; Abstract; Results 3.x p.9","quote":"RB% for F24 to commercial capsule was calculated from the ratio AUC 0-24 test to AUC 0-24 reference and found to be 227%","quoteCheck":"supported","note":""},{"pmid":"32654568","species":"other_animal","arm":"","form":"floating microspheres (HPMC/EC blend, formula F24)","forms":[],"dose":"200 mg (microspheres equivalent to 200 mg silymarin per Methods)","doseBasis":"active compound","fed":"fasted overnight","n":"6","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"text/abstract","value":"1021.3","variance":"","units":"ng/ml","location":"Abstract","quote":"high Cmax (1021.3 ng/ml) and Tmax (6 h)","quoteCheck":"supported","note":"same as Table 10"},{"pmid":"35300217","species":"other_animal","arm":"","form":"silymarin solid dispersion (PEG 6000, alcohol, silymarin API 16.6%, light calcium carbonate); 10% silymarin, 3.92% silybin (developed at South China Agricultural University, produced at Jinhe Bio-Tech)","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound (silybin)","fed":"NR","n":"8","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.48","variance":"± 0.06 (SD)","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"p-value is SD vs PM comparison (independent t-test)"},{"pmid":"35300217","species":"other_animal","arm":"","form":"silymarin premix (3.10% silybin) (Guangzhou Leader Bio-Technology)","forms":["silymarin"],"dose":"50 mg/kg","doseBasis":"active compound (silybin)","fed":"NR","n":"8","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.48","variance":"± 0.06 (SD)","units":"h","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"35300217","species":"other_animal","arm":"","form":"silymarin solid dispersion (PEG 6000, alcohol, silymarin API 16.6%, light calcium carbonate); 10% silymarin, 3.92% silybin (developed at South China Agricultural University, produced at Jinhe Bio-Tech)","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound (silybin)","fed":"NR","n":"8","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1,190.02","variance":"± 246.97 (SD)","units":"ng ml−1","location":"Table 4","quote":"","quoteCheck":"no quote","note":"p-value is SD vs PM comparison (independent t-test); Table 3 and Results text print peak as 1,189.26 (at 0.5 h)"},{"pmid":"35300217","species":"other_animal","arm":"","form":"silymarin premix (3.10% silybin) (Guangzhou Leader Bio-Technology)","forms":["silymarin"],"dose":"50 mg/kg","doseBasis":"active compound (silybin)","fed":"NR","n":"8","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"411.35","variance":"± 84.92 (SD)","units":"ng ml−1","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"35300217","species":"other_animal","arm":"","form":"silymarin solid dispersion (PEG 6000, alcohol, silymarin API 16.6%, light calcium carbonate); 10% silymarin, 3.92% silybin (developed at South China Agricultural University, produced at Jinhe Bio-Tech)","forms":["enhanced"],"dose":"50 mg/kg","doseBasis":"active compound (silybin)","fed":"NR","n":"8","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"1,299.19","variance":"± 67.61 (SD)","units":"ng ml−1 h","location":"Table 4","quote":"","quoteCheck":"no quote","note":"p-value is SD vs PM comparison (independent t-test)"},{"pmid":"35300217","species":"other_animal","arm":"","form":"silymarin premix (3.10% silybin) (Guangzhou Leader Bio-Technology)","forms":["silymarin"],"dose":"50 mg/kg","doseBasis":"active compound (silybin)","fed":"NR","n":"8","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-∞","value":"586.82","variance":"± 180.99 (SD)","units":"ng ml−1 h","location":"Table 4","quote":"","quoteCheck":"no quote","note":""},{"pmid":"37964172","species":"other_animal","arm":"","form":"Pure silymarin (Panjin Huacheng)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Cmax","detail":"Cmax","value":"426.4","variance":"± 192.1 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Pure silymarin (Panjin Huacheng)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Tmax","detail":"Tmax","value":"1.3","variance":"± 1.0 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Pure silymarin (Panjin Huacheng)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"2121.3","variance":"± 696.0 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: b,c. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Pure silymarin (Panjin Huacheng)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"2465.5","variance":"± 706.7 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: c. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin solid dispersion, SM:(PVP K30:F68 3:1) 1:3 w/w","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Cmax","detail":"Cmax","value":"959.8","variance":"± 303.6 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin solid dispersion, SM:(PVP K30:F68 3:1) 1:3 w/w","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Tmax","detail":"Tmax","value":"1.75","variance":"± 0.5 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin solid dispersion, SM:(PVP K30:F68 3:1) 1:3 w/w","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"4884.8","variance":"± 2123.3 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: c. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin solid dispersion, SM:(PVP K30:F68 3:1) 1:3 w/w","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"5318.9","variance":"± 2302.8 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: c. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-soybean lecithin phospholipid complex (SM 4 g : lecithin 7.2 g)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Cmax","detail":"Cmax","value":"1243.4","variance":"± 782.3 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-soybean lecithin phospholipid complex (SM 4 g : lecithin 7.2 g)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Tmax","detail":"Tmax","value":"2.8","variance":"± 0.8 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-soybean lecithin phospholipid complex (SM 4 g : lecithin 7.2 g)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"4987.3","variance":"± 2201.3 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: c. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-soybean lecithin phospholipid complex (SM 4 g : lecithin 7.2 g)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"5182.5","variance":"± 2150.7 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: c. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-SBE-β-CD inclusion complex, molar ratio 1:8","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Cmax","detail":"Cmax","value":"1642.0","variance":"± 477.4 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-SBE-β-CD inclusion complex, molar ratio 1:8","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Tmax","detail":"Tmax","value":"1.5","variance":"± 0.3 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-SBE-β-CD inclusion complex, molar ratio 1:8","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"5174.8","variance":"± 858.01 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: a,c. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-SBE-β-CD inclusion complex, molar ratio 1:8","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"5794.0","variance":"± 797.2 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: a,c. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Self-microemulsifying system: SM:ethanol:Cremophor RH40:ethyl linoleate 0.5:0.5:3.2:1.6","forms":[],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Cmax","detail":"Cmax","value":"3818.5","variance":"± 1331.5 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: a,b"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Self-microemulsifying system: SM:ethanol:Cremophor RH40:ethyl linoleate 0.5:0.5:3.2:1.6","forms":[],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Tmax","detail":"Tmax","value":"1.2","variance":"± 0.3 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Self-microemulsifying system: SM:ethanol:Cremophor RH40:ethyl linoleate 0.5:0.5:3.2:1.6","forms":[],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"13444.8","variance":"± 4393.4 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: a,b. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Self-microemulsifying system: SM:ethanol:Cremophor RH40:ethyl linoleate 0.5:0.5:3.2:1.6","forms":[],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"13820.0","variance":"± 4637.9 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: a,b. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Legalon® (MEDA Pharma) (Legalon®)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Cmax","detail":"Cmax","value":"1219.5","variance":"± 215.5 (SD)","units":"ng/mL","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Legalon® (MEDA Pharma) (Legalon®)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"Tmax","detail":"Tmax","value":"1.6","variance":"± 1.0 (SD)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Legalon® (MEDA Pharma) (Legalon®)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-24","value":"5204.0","variance":"± 1144.1 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: a,c. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Legalon® (MEDA Pharma) (Legalon®)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB; isomers A and B summed)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"5625.6","variance":"± 1020.8 (SD)","units":"ng/L*h","location":"Table 3","quote":"","quoteCheck":"no quote","note":"Table 3 (n = 6, mean ± SD). Silybin (SB) used as benchmark component; plasma treated with β-glucuronidase (total SB). Footnote: a p<0.05 vs SM, b p<0.05 vs Legalon®, c p<0.05 vs SM-SMEDDS. Superscript printed: a,c. AUC unit printed as 'ng/L*h' while Cmax is ng/mL; recorded as printed"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Pure silymarin (Panjin Huacheng)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr1 relative bioavailability vs SM (AUC0-t)","value":"100.0","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Reference arm printed as 100.0; others computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Pure silymarin (Panjin Huacheng)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr2 relative bioavailability vs Legalon® (AUC0-t)","value":"40.8","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin solid dispersion, SM:(PVP K30:F68 3:1) 1:3 w/w","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr1 relative bioavailability vs SM (AUC0-t)","value":"230.3","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin solid dispersion, SM:(PVP K30:F68 3:1) 1:3 w/w","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr2 relative bioavailability vs Legalon® (AUC0-t)","value":"93.9","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-soybean lecithin phospholipid complex (SM 4 g : lecithin 7.2 g)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr1 relative bioavailability vs SM (AUC0-t)","value":"235.1","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-soybean lecithin phospholipid complex (SM 4 g : lecithin 7.2 g)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr2 relative bioavailability vs Legalon® (AUC0-t)","value":"95.8","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-SBE-β-CD inclusion complex, molar ratio 1:8","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr1 relative bioavailability vs SM (AUC0-t)","value":"243.9","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-SBE-β-CD inclusion complex, molar ratio 1:8","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr2 relative bioavailability vs Legalon® (AUC0-t)","value":"99.4","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Self-microemulsifying system: SM:ethanol:Cremophor RH40:ethyl linoleate 0.5:0.5:3.2:1.6","forms":[],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr1 relative bioavailability vs SM (AUC0-t)","value":"633.8","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Self-microemulsifying system: SM:ethanol:Cremophor RH40:ethyl linoleate 0.5:0.5:3.2:1.6","forms":[],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr2 relative bioavailability vs Legalon® (AUC0-t)","value":"258.4","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Legalon® (MEDA Pharma) (Legalon®)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr1 relative bioavailability vs SM (AUC0-t)","value":"245.3","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Legalon® (MEDA Pharma) (Legalon®)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Fr2 relative bioavailability vs Legalon® (AUC0-t)","value":"100.0","variance":"","units":"%","location":"Table 4","quote":"","quoteCheck":"no quote","note":"Reference arm printed as 100.0; others computed by authors from AUC0-t (Eq. 3). Text expresses these as fold values"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin solid dispersion, SM:(PVP K30:F68 3:1) 1:3 w/w","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability vs SM as fold, text","value":"2.30","variance":"","units":"fold higher than SM","location":"Results 3.5.2","quote":"relative bioavailability of SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS and Legalon® was 2.30-fold, 2.35-fold, 2.44-fold, 6.34-fold, and 2.45-fold higher than that of SM","quoteCheck":"supported","note":"Same as Table 4 Fr1 expressed as fold"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-soybean lecithin phospholipid complex (SM 4 g : lecithin 7.2 g)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability vs SM as fold, text","value":"2.35","variance":"","units":"fold higher than SM","location":"Results 3.5.2","quote":"relative bioavailability of SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS and Legalon® was 2.30-fold, 2.35-fold, 2.44-fold, 6.34-fold, and 2.45-fold higher than that of SM","quoteCheck":"supported","note":"Same as Table 4 Fr1 expressed as fold"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-SBE-β-CD inclusion complex, molar ratio 1:8","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability vs SM as fold, text","value":"2.44","variance":"","units":"fold higher than SM","location":"Results 3.5.2","quote":"relative bioavailability of SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS and Legalon® was 2.30-fold, 2.35-fold, 2.44-fold, 6.34-fold, and 2.45-fold higher than that of SM","quoteCheck":"supported","note":"Same as Table 4 Fr1 expressed as fold"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Self-microemulsifying system: SM:ethanol:Cremophor RH40:ethyl linoleate 0.5:0.5:3.2:1.6","forms":[],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability vs SM as fold, text","value":"6.34","variance":"","units":"fold higher than SM","location":"Results 3.5.2","quote":"relative bioavailability of SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS and Legalon® was 2.30-fold, 2.35-fold, 2.44-fold, 6.34-fold, and 2.45-fold higher than that of SM","quoteCheck":"supported","note":"Same as Table 4 Fr1 expressed as fold"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Legalon® (MEDA Pharma) (Legalon®)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability vs SM as fold, text","value":"2.45","variance":"","units":"fold higher than SM","location":"Results 3.5.2","quote":"relative bioavailability of SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS and Legalon® was 2.30-fold, 2.35-fold, 2.44-fold, 6.34-fold, and 2.45-fold higher than that of SM","quoteCheck":"supported","note":"Same as Table 4 Fr1 expressed as fold"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Pure silymarin (Panjin Huacheng)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability vs Legalon® as fold, text","value":"0.41","variance":"","units":"fold higher than Legalon®","location":"Results 3.5.2","quote":"relative bioavailability of SM, SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS was 0.41-fold, 0.94-fold, 0.96-fold, 0.99-fold, and 2.58-fold higher than that of Legalon®","quoteCheck":"supported","note":"Same as Table 4 Fr2 expressed as fold (text says 'higher' even for values <1)"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin solid dispersion, SM:(PVP K30:F68 3:1) 1:3 w/w","forms":["enhanced"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability vs Legalon® as fold, text","value":"0.94","variance":"","units":"fold higher than Legalon®","location":"Results 3.5.2","quote":"relative bioavailability of SM, SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS was 0.41-fold, 0.94-fold, 0.96-fold, 0.99-fold, and 2.58-fold higher than that of Legalon®","quoteCheck":"supported","note":"Same as Table 4 Fr2 expressed as fold (text says 'higher' even for values <1)"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-soybean lecithin phospholipid complex (SM 4 g : lecithin 7.2 g)","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability vs Legalon® as fold, text","value":"0.96","variance":"","units":"fold higher than Legalon®","location":"Results 3.5.2","quote":"relative bioavailability of SM, SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS was 0.41-fold, 0.94-fold, 0.96-fold, 0.99-fold, and 2.58-fold higher than that of Legalon®","quoteCheck":"supported","note":"Same as Table 4 Fr2 expressed as fold (text says 'higher' even for values <1)"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Silymarin-SBE-β-CD inclusion complex, molar ratio 1:8","forms":["silymarin"],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability vs Legalon® as fold, text","value":"0.99","variance":"","units":"fold higher than Legalon®","location":"Results 3.5.2","quote":"relative bioavailability of SM, SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS was 0.41-fold, 0.94-fold, 0.96-fold, 0.99-fold, and 2.58-fold higher than that of Legalon®","quoteCheck":"supported","note":"Same as Table 4 Fr2 expressed as fold (text says 'higher' even for values <1)"},{"pmid":"37964172","species":"other_animal","arm":"","form":"Self-microemulsifying system: SM:ethanol:Cremophor RH40:ethyl linoleate 0.5:0.5:3.2:1.6","forms":[],"dose":"30 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"silybin (SB)","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative bioavailability vs Legalon® as fold, text","value":"2.58","variance":"","units":"fold higher than Legalon®","location":"Results 3.5.2","quote":"relative bioavailability of SM, SM-SD, SM-PC, SM-SBE-β-CDIC, SM-SMEDDS was 0.41-fold, 0.94-fold, 0.96-fold, 0.99-fold, and 2.58-fold higher than that of Legalon®","quoteCheck":"supported","note":"Same as Table 4 Fr2 expressed as fold (text says 'higher' even for values <1)"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"Un-milled silybin coarse powder suspension (Silybin from Nanjing Zelang)","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0−∞)","value":"3.264","variance":"","units":"mg l−1 h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Statistic type not stated (table header: mean pharmacokinetic parameters)"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"High pressure homogenization (800 bar) nanosuspension; particle size 641.8 ± 14.7 nm; freeze-dried with mannitol (Experimental)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0−∞)","value":"7.443","variance":"","units":"mg l−1 h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Statistic type not stated (table header: mean pharmacokinetic parameters)"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"High pressure homogenization (1800 bar) nanosuspension; particle size 127 ± 1.9 nm; freeze-dried with mannitol (Experimental)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0−∞)","value":"9.552","variance":"","units":"mg l−1 h","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Statistic type not stated (table header: mean pharmacokinetic parameters)"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"Un-milled silybin coarse powder suspension (Silybin from Nanjing Zelang)","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.56","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20332565","species":"in_vitro","arm":"","form":"High pressure homogenization (800 bar) nanosuspension; particle size 641.8 ± 14.7 nm; freeze-dried with mannitol (Experimental)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.03","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20332565","species":"in_vitro","arm":"","form":"High pressure homogenization (1800 bar) nanosuspension; particle size 127 ± 1.9 nm; freeze-dried with mannitol (Experimental)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.08","variance":"","units":"h","location":"Table 1","quote":"","quoteCheck":"no quote","note":""},{"pmid":"20332565","species":"in_vitro","arm":"","form":"Un-milled silybin coarse powder suspension (Silybin from Nanjing Zelang)","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel vs un-milled suspension (AUCnanosuspension/AUCcontrol)","value":"100","variance":"","units":"%","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Statistic type not stated (table header: mean pharmacokinetic parameters)"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"High pressure homogenization (800 bar) nanosuspension; particle size 641.8 ± 14.7 nm; freeze-dried with mannitol (Experimental)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel vs un-milled suspension (AUCnanosuspension/AUCcontrol)","value":"228.0","variance":"","units":"%","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Statistic type not stated (table header: mean pharmacokinetic parameters)"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"High pressure homogenization (1800 bar) nanosuspension; particle size 127 ± 1.9 nm; freeze-dried with mannitol (Experimental)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"Frel vs un-milled suspension (AUCnanosuspension/AUCcontrol)","value":"292.6","variance":"","units":"%","location":"Table 1","quote":"","quoteCheck":"no quote","note":"Statistic type not stated (table header: mean pharmacokinetic parameters)"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"Un-milled silybin coarse powder suspension (Silybin from Nanjing Zelang)","forms":[],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.53","variance":"± 0.22 (NR)","units":"μg ml−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":"± type not stated"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"High pressure homogenization (800 bar) nanosuspension; particle size 641.8 ± 14.7 nm; freeze-dried with mannitol (Experimental)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"2.37","variance":"± 0.39 (NR)","units":"μg ml−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":"± type not stated"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"High pressure homogenization (1800 bar) nanosuspension; particle size 127 ± 1.9 nm; freeze-dried with mannitol (Experimental)","forms":["enhanced"],"dose":"20 mg/kg","doseBasis":"active compound","fed":"fasted overnight and ~3 h post-dose","n":"3","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"2.73","variance":"± 0.30 (NR)","units":"μg ml−1","location":"Table 1","quote":"","quoteCheck":"no quote","note":"± type not stated"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"Silybin 1 g in Cremophor EL 2% / 1,2-propylene glycol 1.56% / 0.9% NaCl to 100 mL","forms":[],"dose":"15 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0−∞)","value":"14.088","variance":"","units":"h μg ml−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Statistic type not stated"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"SN-A nanosuspension (Experimental)","forms":["enhanced"],"dose":"15 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0−∞)","value":"41.859","variance":"","units":"h μg ml−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Statistic type not stated"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"SN-B nanosuspension (Experimental)","forms":["enhanced"],"dose":"15 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC(0−∞)","value":"27.701","variance":"","units":"h μg ml−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Statistic type not stated"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"Silybin 1 g in Cremophor EL 2% / 1,2-propylene glycol 1.56% / 0.9% NaCl to 100 mL","forms":[],"dose":"15 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"32.7","variance":"± 4.3 (NR)","units":"μg ml−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"± type not stated. Discussion text on PDF p.12 states SN-B Cmax 32.7 and solution 27.6 (swapped vs Table 2)"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"SN-A nanosuspension (Experimental)","forms":["enhanced"],"dose":"15 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"21.6","variance":"± 5.8 (NR)","units":"μg ml−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"± type not stated. Results text on p.12 states SN-B Cmax 32.7 and solution 27.6 (swapped vs Table 2)"},{"pmid":"20332565","species":"in_vitro","arm":"","form":"SN-B nanosuspension (Experimental)","forms":["enhanced"],"dose":"15 mg/kg","doseBasis":"active compound","fed":"fasted overnight","n":"3","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"27.6","variance":"± 2.7 (NR)","units":"μg ml−1","location":"Table 2","quote":"","quoteCheck":"no quote","note":"± type not stated. Discussion text on PDF p.12 states SN-B Cmax 32.7 and solution 27.6 (swapped vs Table 2)"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"Legalon tablets (Legalon (MADAUS GmbH, Germany))","forms":["silymarin"],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"490.9","variance":"","units":"ng ml-1","location":"Results 3.2 p.2109","quote":"Cmax (490.9 ng ml-1) was reached with Tmax at approximately 1 h","quoteCheck":"supported","note":"Not given in Table 4"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"Legalon tablets (Legalon (MADAUS GmbH, Germany))","forms":["silymarin"],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"approximately 1","variance":"","units":"h","location":"Results 3.2 p.2109","quote":"Cmax (490.9 ng ml-1) was reached with Tmax at approximately 1 h","quoteCheck":"supported","note":"double peak observed (considered enterohepatic circulation by authors)"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"Legalon tablets (Legalon (MADAUS GmbH, Germany))","forms":["silymarin"],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"approximately 3.56","variance":"","units":"µg h ml-1","location":"Results 3.2 p.2110","quote":"AUC0-∞ of commercial tablets drastically increased from approximately 3.56 µg h ml-1","quoteCheck":"supported","note":"Printed as approximate; not in Table 4"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"silymarin SD (PVP K30, lecithin, Eudragit E100)","forms":["silymarin"],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"236.7","variance":"","units":"ng ml-1","location":"Results 3.2 p.2109","quote":"Silymarin SD gave the lowest Cmax (236.7 ng ml-1) at approximately 3 h","quoteCheck":"supported","note":""},{"pmid":"22343518","species":"in_vitro","arm":"","form":"silymarin SD (PVP K30, lecithin, Eudragit E100)","forms":["silymarin"],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"approximately 3","variance":"","units":"h","location":"Results 3.2 p.2109","quote":"Silymarin SD gave the lowest Cmax (236.7 ng ml-1) at approximately 3 h","quoteCheck":"supported","note":"plasma silybin below HPLC detection limit at 24 h"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"silymarin SD (PVP K30, lecithin, Eudragit E100)","forms":["silymarin"],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative to commercial tablets, F(%) dose-normalised AUC ratio","value":"29.6","variance":"","units":"%","location":"Results 3.2 p.2110","quote":"relative bioavailability of silymarin SD was found to be only 29.6%","quoteCheck":"supported","note":"Comparator inferred from Methods Eq. 1 and context (reference = commercial tablets)"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"silymarin-loaded PSNs","forms":["silymarin"],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"241.2","variance":"","units":"ng/ml","location":"Table 4","quote":"Silymarin-loaded PSNs 21.2 241.2 24 22.3 14330.1","quoteCheck":"supported","note":"Text p.2109 also gives 241.2 ng ml-1"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"silymarin-loaded PSNs","forms":["silymarin"],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"24","variance":"","units":"h","location":"Table 4","quote":"Silymarin-loaded PSNs 21.2 241.2 24 22.3 14330.1","quoteCheck":"supported","note":"Text: Cmax seen at 24 h after administration"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"silymarin-loaded PSNs","forms":["silymarin"],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"14330.1","variance":"","units":"ng h/ml","location":"Table 4","quote":"Silymarin-loaded PSNs 21.2 241.2 24 22.3 14330.1","quoteCheck":"supported","note":"Text p.2110 gives 'approximately 14.3 µg h ml-1' (same value)"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"silymarin-loaded PSNs","forms":["silymarin"],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf (text)","value":"approximately 14.3","variance":"","units":"µg h ml-1","location":"Results 3.2 p.2110","quote":"approximately 3.56 µg h ml-1 to approximately 14.3 and 25.8 µg h ml-1 for drug-loaded PSNs","quoteCheck":"supported","note":""},{"pmid":"22343518","species":"in_vitro","arm":"","form":"silymarin-loaded PSNs","forms":["silymarin"],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative to commercial tablets","value":"approximately 323.9","variance":"","units":"%","location":"Results 3.2 p.2110","quote":"that of silymarin-loaded PSNs was approximately 323.9%","quoteCheck":"supported","note":"Printed as approximate"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"3-day release capsule","forms":[],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"338.1","variance":"","units":"ng/ml","location":"Table 4","quote":"3-Day release formulation 21.2 338.1 10 54.3 25819.4","quoteCheck":"supported","note":"Text p.2109-2110 gives 338.12 ng ml-1"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"3-day release capsule","forms":[],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"Cmax","detail":"text value","value":"338.12","variance":"","units":"ng ml-1","location":"Results 3.2 p.2110","quote":"Cmax and Tmax of the 3-day release formulation were 338.12 ng ml-1 and 10 h, respectively","quoteCheck":"supported","note":"Table 4 prints 338.1"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"3-day release capsule","forms":[],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"10","variance":"","units":"h","location":"Table 4 and Results 3.2 p.2110","quote":"Cmax and Tmax of the 3-day release formulation were 338.12 ng ml-1 and 10 h, respectively","quoteCheck":"supported","note":""},{"pmid":"22343518","species":"in_vitro","arm":"","form":"3-day release capsule","forms":[],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"25819.4","variance":"","units":"ng h/ml","location":"Table 4","quote":"3-Day release formulation 21.2 338.1 10 54.3 25819.4","quoteCheck":"supported","note":"Text gives approximately 25.8 µg h ml-1"},{"pmid":"22343518","species":"in_vitro","arm":"","form":"3-day release capsule","forms":[],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf (text)","value":"approximately 25.8","variance":"","units":"µg h ml-1","location":"Results 3.2 p.2110","quote":"approximately 14.3 and 25.8 µg h ml-1 for drug-loaded PSNs and the 3-day release formulation","quoteCheck":"value not in quote","note":""},{"pmid":"22343518","species":"in_vitro","arm":"","form":"3-day release capsule","forms":[],"dose":"21.2 mg/kg","doseBasis":"NR","fed":"fasted overnight","n":"6","analyte":"plasma silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"relative to commercial tablets","value":"448.2","variance":"","units":"%","location":"Results 3.2 p.2110","quote":"relative oral bioavailability of the 3-day release formulation was 448.2%","quoteCheck":"supported","note":""},{"pmid":"22530301","species":"in_vitro","arm":"","form":"pure silymarin in capsules","forms":["silymarin"],"dose":"280 mg/kg silymarin","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"250.62","variance":"± 85.44 (SEM)","units":"µg/ml","location":"Table 2","quote":"Cmax (µg/ml) 250.62 ± 85.44","quoteCheck":"supported","note":"Table 2 header says Cmax unit µg/ml; text says mean ± S.E. (Methods/Results), Table 2 itself prints ± without stating type"},{"pmid":"22530301","species":"in_vitro","arm":"","form":"pure silymarin in capsules","forms":["silymarin"],"dose":"280 mg/kg silymarin","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.20","variance":"± 0.29 (SEM)","units":"h","location":"Table 2","quote":"Tmax (h) 1.20 ± 0.29","quoteCheck":"supported","note":""},{"pmid":"22530301","species":"in_vitro","arm":"","form":"pure silymarin in capsules","forms":["silymarin"],"dose":"280 mg/kg silymarin","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-12","value":"587.53","variance":"± 43.65 (SEM)","units":"g.h/ml","location":"Table 2","quote":"AUC0–12 (g.h/ml) 587.53 ± 43.65","quoteCheck":"supported","note":"Table 2 prints unit as 'g.h/ml' (page image checked); text says µg h/ml for SP"},{"pmid":"22530301","species":"in_vitro","arm":"","form":"Hepaticum capsules (Hepaticum)","forms":[],"dose":"280 mg/kg silymarin (same equivalent amount)","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1462.10","variance":"± 285.6 (SEM)","units":"µg/ml","location":"Table 2","quote":"1462.10a ± 285.6","quoteCheck":"supported","note":"Table 2 header says Cmax unit µg/ml; text says mean ± S.E. (Methods/Results), Table 2 itself prints ± without stating type; a = significantly different from silymarin capsules"},{"pmid":"22530301","species":"in_vitro","arm":"","form":"Hepaticum capsules (Hepaticum)","forms":[],"dose":"280 mg/kg silymarin (same equivalent amount)","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.13","variance":"± 0.3 (SEM)","units":"h","location":"Table 2","quote":"Tmax (h) 1.13 ± 0.3","quoteCheck":"supported","note":""},{"pmid":"22530301","species":"in_vitro","arm":"","form":"Hepaticum capsules (Hepaticum)","forms":[],"dose":"280 mg/kg silymarin (same equivalent amount)","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-12","value":"4891.7","variance":"± 301 (SEM)","units":"g.h/ml","location":"Table 2","quote":"4891.7a ± 301","quoteCheck":"supported","note":"Unit printed 'g.h/ml'; a = significantly different from silymarin capsules"},{"pmid":"22530301","species":"in_vitro","arm":"","form":"silymarin-Gelucire 44/14 SD","forms":["silymarin"],"dose":"280 mg/kg silymarin","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1523.96","variance":"± 350.2 (SEM)","units":"µg/ml","location":"Table 2","quote":"1523.96a ± 350.2","quoteCheck":"supported","note":"Table 2 header says Cmax unit µg/ml; text says mean ± S.E. (Methods/Results), Table 2 itself prints ± without stating type; a = significantly different from silymarin capsules"},{"pmid":"22530301","species":"in_vitro","arm":"","form":"silymarin-Gelucire 44/14 SD","forms":["silymarin"],"dose":"280 mg/kg silymarin","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.01","variance":"± 0.29 (SEM)","units":"h","location":"Table 2","quote":"Tmax (h) 1.01 ± 0.29","quoteCheck":"supported","note":""},{"pmid":"22530301","species":"in_vitro","arm":"","form":"silymarin-Gelucire 44/14 SD","forms":["silymarin"],"dose":"280 mg/kg silymarin","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-12","value":"7643.01","variance":"± 447.3 (SEM)","units":"g.h/ml","location":"Table 2","quote":"7643.01a,b ± 447.3","quoteCheck":"supported","note":"Unit printed 'g.h/ml'; a = sig. different from silymarin capsules, b = sig. different from commercial product capsule"},{"pmid":"22530301","species":"in_vitro","arm":"","form":"pure silymarin in capsules","forms":["silymarin"],"dose":"280 mg/kg silymarin","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-12 (text)","value":"587.5","variance":"","units":"µg h/ml","location":"Results p.212","quote":"SP capsules showed the lowest silybin plasma level with AUC0–12 of only 587.5 µg h/ml","quoteCheck":"supported","note":"Text rounding of Table 2 value; text unit µg h/ml vs Table 2 'g.h/ml'"},{"pmid":"22530301","species":"in_vitro","arm":"","form":"pure silymarin in capsules","forms":["silymarin"],"dose":"280 mg/kg silymarin","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"(text)","value":"250.62","variance":"","units":"µg/ml","location":"Results p.212","quote":"Cmax of 250.62 µg/ml","quoteCheck":"supported","note":""},{"pmid":"22530301","species":"in_vitro","arm":"","form":"silymarin-Gelucire 44/14 SD","forms":["silymarin"],"dose":"280 mg/kg silymarin","doseBasis":"NR","fed":"fasted 24 h","n":"NR","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"AUC0-12 ratio GL/CP","value":"156.2","variance":"","units":"%","location":"Results p.212; Abstract","quote":"The relative bioavailability of GL to cyclodextrin CP was 156.2%","quoteCheck":"supported","note":""},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-NLC (Precirol ATO-5, oleic acid, lecithin, Tween-80)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.86","variance":"± 0.34 (NR)","units":"µg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2; * p<0.05 vs Legalon; # p<0.05 vs SM solid dispersion pellets"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"Legalon capsule (Legalon (Madaus AG))","forms":["silymarin"],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.22","variance":"± 0.07 (NR)","units":"µg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-pellets in hard gelatin capsules (self-made)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.25","variance":"± 0.08 (NR)","units":"µg/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-NLC (Precirol ATO-5, oleic acid, lecithin, Tween-80)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.71","variance":"± 0.33 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"Legalon capsule (Legalon (Madaus AG))","forms":["silymarin"],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.54","variance":"± 0.68 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-pellets in hard gelatin capsules (self-made)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.13","variance":"± 1.02 (NR)","units":"h","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-NLC (Precirol ATO-5, oleic acid, lecithin, Tween-80)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h","value":"1.12","variance":"± 0.28 (NR)","units":"µg h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2; * p<0.05 vs Legalon; # p<0.05 vs SM solid dispersion pellets"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"Legalon capsule (Legalon (Madaus AG))","forms":["silymarin"],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h","value":"0.44","variance":"± 0.12 (NR)","units":"µg h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-pellets in hard gelatin capsules (self-made)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-8h","value":"0.36","variance":"± 0.06 (NR)","units":"µg h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-NLC (Precirol ATO-5, oleic acid, lecithin, Tween-80)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"1.21","variance":"± 0.30 (NR)","units":"µg h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2; * p<0.05 vs Legalon; # p<0.05 vs SM solid dispersion pellets"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"Legalon capsule (Legalon (Madaus AG))","forms":["silymarin"],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"0.52","variance":"± 0.16 (NR)","units":"µg h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-pellets in hard gelatin capsules (self-made)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"AUC","detail":"AUC0-inf","value":"0.54","variance":"± 0.23 (NR)","units":"µg h/mL","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-NLC (Precirol ATO-5, oleic acid, lecithin, Tween-80)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"relative_bioavailability","detail":"RBA vs Legalon, AUC0-8h","value":"253.60","variance":"± 63.64 (NR)","units":"%","location":"Table 2","quote":"2.54-fold that of marketed Legalon capsules","quoteCheck":"value not in quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2; * p<0.05 vs Legalon; # p<0.05 vs SM solid dispersion pellets; row 1 of RBA (reference = Legalon 100)"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-NLC (Precirol ATO-5, oleic acid, lecithin, Tween-80)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"relative_bioavailability","detail":"RBA vs SM-pellets, AUC0-8h","value":"310.38","variance":"± 77.78 (NR)","units":"%","location":"Table 2","quote":"3.10-fold that of self-made SM-pellets","quoteCheck":"value not in quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2; * p<0.05 vs Legalon; # p<0.05 vs SM solid dispersion pellets; row 2 of RBA (reference = SM-pellets 100)"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"Legalon capsule (Legalon (Madaus AG))","forms":["silymarin"],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"relative_bioavailability","detail":"RBA of Legalon vs SM-pellets, AUC0-8h","value":"122.22","variance":"± 33.33 (NR)","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2; row 2 of RBA"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-pellets in hard gelatin capsules (self-made)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"relative_bioavailability","detail":"RBA of SM-pellets vs Legalon, AUC0-8h","value":"81.82","variance":"± 13.64 (NR)","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"Table 2 image shows µg/mL and µg h/mL (text layer prints mg/mL; Fig. 7 axis and text print mg/ml); '±' value type not stated for Table 2; row 1 of RBA"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"Legalon capsule (Legalon (Madaus AG))","forms":["silymarin"],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"relative_bioavailability","detail":"Legalon reference value","value":"100","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"reference row 1"},{"pmid":"24008629","species":"in_vitro","arm":"","form":"SM-pellets in hard gelatin capsules (self-made)","forms":[],"dose":"8 mg/kg (equivalent dose based on silybin)","doseBasis":"active compound","fed":"fasted","n":"6","analyte":"silybin (as marker of silymarin)","matrix":"plasma","parameter":"relative_bioavailability","detail":"SM-pellets reference value","value":"100","variance":"","units":"%","location":"Table 2","quote":"","quoteCheck":"no quote","note":"reference row 2"},{"pmid":"26674103","species":"in_vitro","arm":"","form":"silymarin proliposome (1 g silymarin, 10 g soy lecithin, 5 g cholesterol, 0.5 g sodium oleate in 100 mL propylene glycol); 1 mL added to 10 mL distilled water","forms":["enhanced"],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"5","analyte":"silymarin (UV 288 nm)","matrix":"serosal fluid (everted rat intestinal sac)","parameter":"AUC","detail":"AUC of serosal absorption (trapezoidal method); interval not labelled in Table 5","value":"2.679","variance":"","units":"(µg/ml)*min (×10^3)","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Column header printed as 'AUC (μg/ml)*min (×103)'; value given without variance."},{"pmid":"26674103","species":"in_vitro","arm":"","form":"same amount of silymarin dissolved in propylene glycol, 1 mL added to 10 mL distilled water","forms":["silymarin"],"dose":"NR NR","doseBasis":"NR","fed":"NR","n":"5","analyte":"silymarin (UV 288 nm)","matrix":"serosal fluid (everted rat intestinal sac)","parameter":"AUC","detail":"AUC of serosal absorption (trapezoidal method); interval not labelled in Table 5","value":"1.522","variance":"","units":"(µg/ml)*min (×10^3)","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Column header printed as 'AUC (μg/ml)*min (×103)'; value given without variance."},{"pmid":"30448315","species":"in_vitro","arm":"","form":"Legalon 70 mg sugar-coated tablet (Meda), ground and sieved, suspended in distilled water (Legalon)","forms":["silymarin"],"dose":"~28 mg/kg silybin (standardized dose approx.)","doseBasis":"active compound","fed":"fasted 24 h","n":"4","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.40","variance":"± 0.21 (SE)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30448315","species":"in_vitro","arm":"","form":"Legalon 70 mg sugar-coated tablet (Meda), ground and sieved, suspended in distilled water (Legalon)","forms":["silymarin"],"dose":"~28 mg/kg silybin (standardized dose approx.)","doseBasis":"active compound","fed":"fasted 24 h","n":"4","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"2.23","variance":"± 0.47 (SE)","units":"ng/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30448315","species":"in_vitro","arm":"","form":"Legalon 70 mg sugar-coated tablet (Meda), ground and sieved, suspended in distilled water (Legalon)","forms":["silymarin"],"dose":"~28 mg/kg silybin (standardized dose approx.)","doseBasis":"active compound","fed":"fasted 24 h","n":"4","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"21.30","variance":"± 8.57 (SE)","units":"ng.h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30448315","species":"in_vitro","arm":"","form":"supersaturatable self-nanoemulsifying drug delivery system containing milk thistle extract (silymarin 55.8%); exact composition used in PK not itemized in PK section (abstract: optimized with 10% Poloxamer 407)","forms":["enhanced"],"dose":"~28 mg/kg silybin (standardized dose approx.)","doseBasis":"active compound","fed":"fasted 24 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Tmax","detail":"","value":"0.35","variance":"± 0.06 (SE)","units":"h","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30448315","species":"in_vitro","arm":"","form":"supersaturatable self-nanoemulsifying drug delivery system containing milk thistle extract (silymarin 55.8%); exact composition used in PK not itemized in PK section (abstract: optimized with 10% Poloxamer 407)","forms":["enhanced"],"dose":"~28 mg/kg silybin (standardized dose approx.)","doseBasis":"active compound","fed":"fasted 24 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"Cmax","detail":"","value":"115.56","variance":"± 32.53 (SE)","units":"ng/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30448315","species":"in_vitro","arm":"","form":"supersaturatable self-nanoemulsifying drug delivery system containing milk thistle extract (silymarin 55.8%); exact composition used in PK not itemized in PK section (abstract: optimized with 10% Poloxamer 407)","forms":["enhanced"],"dose":"~28 mg/kg silybin (standardized dose approx.)","doseBasis":"active compound","fed":"fasted 24 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h","value":"161.87","variance":"± 24.83 (SE)","units":"ng.h/ml","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30448315","species":"in_vitro","arm":"","form":"supersaturatable self-nanoemulsifying drug delivery system containing milk thistle extract (silymarin 55.8%); exact composition used in PK not itemized in PK section (abstract: optimized with 10% Poloxamer 407)","forms":["enhanced"],"dose":"~28 mg/kg silybin (standardized dose approx.)","doseBasis":"active compound","fed":"fasted 24 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h ratio S-SNEDDS/Legalon, 90% CI lower (log-transformed)","value":"398.83","variance":"","units":"%","location":"Table 3","quote":"","quoteCheck":"no quote","note":"CI-lower; log-transformed per footnote; no point estimate of the ratio printed in table"},{"pmid":"30448315","species":"in_vitro","arm":"","form":"supersaturatable self-nanoemulsifying drug delivery system containing milk thistle extract (silymarin 55.8%); exact composition used in PK not itemized in PK section (abstract: optimized with 10% Poloxamer 407)","forms":["enhanced"],"dose":"~28 mg/kg silybin (standardized dose approx.)","doseBasis":"active compound","fed":"fasted 24 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"AUC","detail":"AUC0-24h ratio S-SNEDDS/Legalon, 90% CI upper (log-transformed)","value":"2430.63","variance":"","units":"%","location":"Table 3","quote":"","quoteCheck":"no quote","note":""},{"pmid":"30448315","species":"in_vitro","arm":"","form":"supersaturatable self-nanoemulsifying drug delivery system containing milk thistle extract (silymarin 55.8%); exact composition used in PK not itemized in PK section (abstract: optimized with 10% Poloxamer 407)","forms":["enhanced"],"dose":"~28 mg/kg silybin (standardized dose approx.)","doseBasis":"active compound","fed":"fasted 24 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"S-SNEDDS vs Legalon (mean)","value":"760 (%)","variance":"","units":"%","location":"Table 3; Abstract","quote":"The relative bioavailability of S-SNEDDS versus Legalon® was about 760%.","quoteCheck":"value not in quote","note":"In Table 3 the 760 (%) value is printed in the Legalon column"},{"pmid":"30448315","species":"in_vitro","arm":"","form":"supersaturatable self-nanoemulsifying drug delivery system containing milk thistle extract (silymarin 55.8%); exact composition used in PK not itemized in PK section (abstract: optimized with 10% Poloxamer 407)","forms":["enhanced"],"dose":"~28 mg/kg silybin (standardized dose approx.)","doseBasis":"active compound","fed":"fasted 24 h","n":"5","analyte":"silybin","matrix":"plasma","parameter":"relative_bioavailability","detail":"S-SNEDDS vs Legalon expressed in fold","value":"7.6","variance":"","units":"fold","location":"Discussion (p.74)","quote":"oral bioavailability of silybin after administration of S-SNEDDS (7.6 folds) compared to Legalon","quoteCheck":"supported","note":""},{"pmid":"30502425","species":"in_vitro","arm":"","form":"silybin solution (Table 5/Fig. 6F); Methods 2.13 lists 'silybin raw powder' as the intravenous control","forms":[],"dose":"10 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma (rabbit, IV administration)","parameter":"AUC","detail":"AUC(0-t)","value":"7.818","variance":"± 1.415 (SD)","units":"μg/L*h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Intravenous administration (route per Methods 2.13 and Table 5 caption)"},{"pmid":"30502425","species":"in_vitro","arm":"","form":"silybin PEG-CS nanocrystals","forms":["enhanced"],"dose":"10 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma (rabbit, IV administration)","parameter":"AUC","detail":"AUC(0-t)","value":"20.224","variance":"± 5.229 (SD)","units":"μg/L*h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Intravenous administration (route per Methods 2.13 and Table 5 caption)"},{"pmid":"30502425","species":"in_vitro","arm":"","form":"silybin nanocaged PEG-CS nanocrystals (mPEG-b-PCL carrier)","forms":["enhanced"],"dose":"10 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma (rabbit, IV administration)","parameter":"AUC","detail":"AUC(0-t)","value":"43.361","variance":"± 8.726 (SD)","units":"μg/L*h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Intravenous administration (route per Methods 2.13 and Table 5 caption)"},{"pmid":"30502425","species":"in_vitro","arm":"","form":"silybin solution (Table 5/Fig. 6F); Methods 2.13 lists 'silybin raw powder' as the intravenous control","forms":[],"dose":"10 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma (rabbit, IV administration)","parameter":"Cmax","detail":"","value":"9.369","variance":"± 2.144 (SD)","units":"μg/L","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Intravenous administration (route per Methods 2.13 and Table 5 caption)"},{"pmid":"30502425","species":"in_vitro","arm":"","form":"silybin PEG-CS nanocrystals","forms":["enhanced"],"dose":"10 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma (rabbit, IV administration)","parameter":"Cmax","detail":"","value":"9.879","variance":"± 2.153 (SD)","units":"μg/L","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Intravenous administration (route per Methods 2.13 and Table 5 caption)"},{"pmid":"30502425","species":"in_vitro","arm":"","form":"silybin nanocaged PEG-CS nanocrystals (mPEG-b-PCL carrier)","forms":["enhanced"],"dose":"10 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma (rabbit, IV administration)","parameter":"Cmax","detail":"","value":"10.292","variance":"± 2.435 (SD)","units":"μg/L","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Intravenous administration (route per Methods 2.13 and Table 5 caption)"},{"pmid":"30502425","species":"in_vitro","arm":"","form":"silybin nanocaged PEG-CS nanocrystals (mPEG-b-PCL carrier)","forms":["enhanced"],"dose":"10 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma (rabbit, IV administration)","parameter":"relative_bioavailability","detail":"AUC fold vs silybin solution (Abstract)","value":"5.54","variance":"","units":"fold","location":"Abstract","quote":"nanocaged nanocrystals and the PEG-CS nanocrystals drug delivery system also exhibited 5.54 and 2.58 fold increasing in the AUC","quoteCheck":"supported","note":"Intravenous; Abstract order: nanocaged 5.54, PEG-CS 2.58 (vs silybin solution). Results text 3.11 gives 2.1 and 5.5 (inconsistent)"},{"pmid":"30502425","species":"in_vitro","arm":"","form":"silybin PEG-CS nanocrystals","forms":["enhanced"],"dose":"10 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma (rabbit, IV administration)","parameter":"relative_bioavailability","detail":"AUC fold vs silybin solution (Abstract)","value":"2.58","variance":"","units":"fold","location":"Abstract","quote":"5.54 and 2.58 fold increasing in the AUC, respectively","quoteCheck":"supported","note":"Intravenous"},{"pmid":"30502425","species":"in_vitro","arm":"","form":"silybin nanocaged PEG-CS nanocrystals (mPEG-b-PCL carrier)","forms":["enhanced"],"dose":"10 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma (rabbit, IV administration)","parameter":"relative_bioavailability","detail":"AUC increase vs silybin solution (Results 3.11 text)","value":"2.1","variance":"","units":"times","location":"Results 3.11","quote":"AUC of the nanocaged nanocrystals significantly increased by 2.1 times and 5.5 times compared to the silybin solution and the PEG-CS nanocrystals, respectively","quoteCheck":"supported","note":"As printed; Table 5 AUC values (43.361 vs 7.818 and vs 20.224) and Abstract (5.54) are inconsistent with this ordering; not resolved"},{"pmid":"30502425","species":"in_vitro","arm":"","form":"silybin nanocaged PEG-CS nanocrystals (mPEG-b-PCL carrier)","forms":["enhanced"],"dose":"10 mg/kg silybin","doseBasis":"active compound","fed":"fasted 12 h","n":"3","analyte":"silybin","matrix":"plasma (rabbit, IV administration)","parameter":"relative_bioavailability","detail":"AUC increase vs PEG-CS nanocrystals (Results 3.11 text)","value":"5.5","variance":"","units":"times","location":"Results 3.11","quote":"increased by 2.1 times and 5.5 times compared to the silybin solution and the PEG-CS nanocrystals, respectively","quoteCheck":"supported","note":"As printed; inconsistent with Table 5"},{"pmid":"36985575","species":"in_vitro","arm":"","form":"Conventional silymarin capsule (Hepavitum, nutraceutical) (Hepavitum)","forms":["silymarin"],"dose":"200 mg/kg (Table 5 column)","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"1.0","variance":"± 0.08 (NR)","units":"h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"+/- value printed without stating SD or SEM; text (2.10) gives conventional Tmax 1.0 h without +/-"},{"pmid":"36985575","species":"in_vitro","arm":"","form":"Conventional silymarin capsule (Hepavitum, nutraceutical) (Hepavitum)","forms":["silymarin"],"dose":"200 mg/kg (Table 5 column)","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"0.6","variance":"± 0.11 (NR)","units":"µg/mL","location":"Table 5","quote":"Cmax for the conventional form was 0.6 ± 0.11 µg mL−1","quoteCheck":"supported","note":""},{"pmid":"36985575","species":"in_vitro","arm":"","form":"Conventional silymarin capsule (Hepavitum, nutraceutical) (Hepavitum)","forms":["silymarin"],"dose":"200 mg/kg (Table 5 column)","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"2.4","variance":"± 0.70 (NR)","units":"µg·h/mL","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 header AUC0-t; text 2.10 says 'area under the curve' (units µg·h mL−1)"},{"pmid":"36985575","species":"in_vitro","arm":"","form":"Gastro-retentive floating tablet: silymarin 200 mg, HPMC K4 100 mg, HPMC K15 120 mg, Carbopol 934p 25 mg, NaHCO3 70 mg, citric acid 10 mg, Mg stearate 5 mg (Table 7)","forms":["silymarin"],"dose":"200 mg/kg (Table 5 column)","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Tmax","detail":"","value":"4.0","variance":"± 0.12 (NR)","units":"h","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Text 2.10 gives formulation Tmax 4.0 h without +/-"},{"pmid":"36985575","species":"in_vitro","arm":"","form":"Gastro-retentive floating tablet: silymarin 200 mg, HPMC K4 100 mg, HPMC K15 120 mg, Carbopol 934p 25 mg, NaHCO3 70 mg, citric acid 10 mg, Mg stearate 5 mg (Table 7)","forms":["silymarin"],"dose":"200 mg/kg (Table 5 column)","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"Cmax","detail":"","value":"1.1","variance":"± 0.42 (NR)","units":"µg/mL","location":"Table 5","quote":"it was 1.1 ± 0.42 µg mL−1 for the formulation","quoteCheck":"supported","note":""},{"pmid":"36985575","species":"in_vitro","arm":"","form":"Gastro-retentive floating tablet: silymarin 200 mg, HPMC K4 100 mg, HPMC K15 120 mg, Carbopol 934p 25 mg, NaHCO3 70 mg, citric acid 10 mg, Mg stearate 5 mg (Table 7)","forms":["silymarin"],"dose":"200 mg/kg (Table 5 column)","doseBasis":"NR","fed":"NR","n":"6","analyte":"silymarin","matrix":"plasma","parameter":"AUC","detail":"AUC0-t","value":"7.5","variance":"± 1.26 (NR)","units":"µg·h/mL","location":"Table 5","quote":"","quoteCheck":"no quote","note":"Table 5 header AUC0-t"}],"studies":{"3398694":{"pmid":"3398694","title":"Silymarin improves metabolism and disposition of aspirin in cirrhotic rats.","authors":"Mourelle M, Favari L","journal":"Life sciences","year":"1988","volume":"43","issue":"3","pages":"201-7","doi":"10.1016/0024-3205(88)90309-8","url":"https://pubmed.ncbi.nlm.nih.gov/3398694/","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, animal experiment)","n":"NR","status":"off-target analyte","statusNote":"Measured compounds are aspirin (ASA) and its salicylate metabolites; silymarin is only the hepatoprotective intervention and its own absorption/levels were not measured. ASA given i.p. in CCl4-cirrhotic rats with/without oral silymarin.","conclusion":"The simultaneous administration of silymarin (50 mg/kg of b.w.) along with CCl4 completely prevented all the alterations.","limitations":"off-target analyte (aspirin/salicylates; silymarin not measured); animal cirrhosis model; i.p. ASA, so no oral absorption of silymarin assessed; most metabolite data figure-only (Fig. 1); absorption assumed instantaneous in half-life model; n of analysed animals not stated beyond 10 per group"},"6870500":{"pmid":"6870500","title":"[Bioavailability of silymarin, 3: splitting of silybin dihemisuccinate by plasma and liver esterases].","authors":"Koch H, Tscherny J","journal":"Archiv der Pharmazie","year":"1983","volume":"316","issue":"5","pages":"426-30","doi":"10.1002/ardp.19833160508","url":"https://pubmed.ncbi.nlm.nih.gov/6870500/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro enzyme incubation)","n":"NR","status":"complete","statusNote":"In vitro enzymatic hydrolysis (bovine plasma vs rat liver homogenate) of the silybin prodrug silybin dihemisuccinate to silybin; no in vivo absorption data.","conclusion":"The conclusion is therefore justified: the succinic acid hemiesters of the silymarin substances fulfil the requirements commonly associated with the term 'prodrug'. (translated from German)","limitations":"in vitro only; bovine plasma and rat liver, not human; figures not quantified; half-lives read from scheme diagrams"},"7283681":{"pmid":"7283681","title":"[Bioavailability of silymarin, I: Volumes of distribution of silybin, silydianin, and silychristin from in-vitro data (author's transl)].","authors":"Koch HP, Ritschel WA","journal":"Archiv der Pharmazie","year":"1981","volume":"314","issue":"6","pages":"515-7","doi":"10.1002/ardp.19813140608","url":"https://pubmed.ncbi.nlm.nih.gov/7283681/","species":"in_vitro","speciesRaw":"in vitro","design":"other (calculation from in-vitro data)","n":"NR","status":"partial","statusNote":"Not an in vivo absorption study: theoretical volumes of distribution of silymarin constituents calculated from in-vitro albumin binding and partition coefficient. No absorption/bioavailability data despite title. Extracted calculated Vd values only.","conclusion":"Such calculations based on data obtained in vitro cannot and are not intended to replace in-vivo pharmacokinetic studies (translated from: 'derartige Berechnungen, die auf in vitro gewonnenen Daten beruhen, nicht die Untersuchung der Pharmakokinetik in vivo ersetzen konnen oder sollen').","limitations":"no in vivo data; values calculated by regression equations, not measured; no absorption or bioavailability parameters; German-language paper"},"9008269":{"pmid":"9008269","title":"Effect of portal vein ligation and silymarin treatment on aspirin metabolism and disposition in rats.","authors":"Favari L, Soto C, Mourelle M","journal":"Biopharmaceutics & drug disposition","year":"1997","volume":"18","issue":"1","pages":"53-64","doi":"10.1002/(sici)1099-081x(199701)18:1<53::aid-bdd3>3.0.co;2-9","url":"https://pubmed.ncbi.nlm.nih.gov/9008269/","species":"rodent","speciesRaw":"rodent","design":"other (controlled animal study, parallel groups)","n":"NR","status":"off-target analyte","statusNote":"Measured analyte is aspirin (total salicylates in plasma, urinary aspirin metabolites) in portal-vein-ligated rats; silymarin was given only as a 7-day pretreatment and was not measured. No silymarin absorption/PK data. Aspirin PK values recorded for reference.","conclusion":"Silymarin markedly reversed the alterations found in the PVL group.","limitations":"silymarin not measured (aspirin is the analyte); n=5 per group; rats; PVL model; silymarin product/purity NR; per-group urinary metabolite values figure-only; tmax printed without variance"},"11529693":{"pmid":"11529693","title":"Pharmacokinetic study of iodine-labeled silibinins in rat.","authors":"Skottová N, SVagera Z, Vecera R, Urbánek K, Jegorov A, Simánek V","journal":"Pharmacological research","year":"2001","volume":"44","issue":"3","pages":"247-53","doi":"10.1006/phrs.2001.0854","url":"https://pubmed.ncbi.nlm.nih.gov/11529693/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"partial","statusNote":"Radiolabeled (125I) silibinin derivatives and phosphatidylcholine complexes in rat; only some values printed in text, most data figure-only (Figs 1-4)","conclusion":"the results of this study suggest that 125I bound to silibinin separated as 125I-SB1 does not significantly change (at least at the low dose of unlabeled silibinin) the properties of labeled silibinin as far as its bioavailability and organ distribution are concerned. Thus, the use of 125I-SB1 should be considered as an option for pharmacokinetic studies of bioavailability of silibinin and its derivatives in experimental animals.","limitations":"radioactivity measured, not parent silibinin; iodinated derivatives may differ from silibinin; small n per arm (3-5); most results figure-only; AUC units from figure caption; anaesthetized animals"},"11883719":{"pmid":"11883719","title":"Silybin and its bioavailable phospholipid complex (IdB 1016) potentiate in vitro and in vivo the activity of cisplatin.","authors":"Giacomelli S, Gallo D, Apollonio P, Ferlini C, Distefano M, Morazzoni P, Riva A, Bombardelli E, Mancuso S, Scambia G","journal":"Life sciences","year":"2002","volume":"70","issue":"12","pages":"1447-59","doi":"10.1016/s0024-3205(01)01511-9","url":"https://pubmed.ncbi.nlm.nih.gov/11883719/","species":"in_vitro","speciesRaw":"in vitro","design":"other (specify)","n":"NR","status":"not absorption-related","statusNote":"Anticancer pharmacodynamic study (A2780 cell growth, apoptosis, nude mouse xenografts, Matrigel angiogenesis) of silybin and IdB 1016 with cisplatin; whole paper read, no plasma/tissue concentration, absorption or PK data reported (bioavailability only mentioned in Introduction/Discussion with references to other studies)","conclusion":"NR (not absorption related; the Abstract reports that silybin and IdB 1016 enhanced cisplatin antitumour activity in vitro and in vivo)","limitations":"not an absorption/PK study"},"12748991":{"pmid":"12748991","title":"Plasma lipoproteins in transport of silibinin, an antioxidant flavonolignan from Silybum marianum.","authors":"Svagera Z, Skottová N, Vána P, Vecera R, Urbánek K, Belejová M, Kosina P, Simánek V","journal":"Phytotherapy research : PTR","year":"2003","volume":"17","issue":"5","pages":"524-30","doi":"10.1002/ptr.1187","url":"https://pubmed.ncbi.nlm.nih.gov/12748991/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"complete","statusNote":"Rat study using 125I-labelled silibinin and silibinin-phosphatidylcholine complex; measures radioactivity and (in one experiment) unlabelled silibinin by HPLC; several time-course data figure-only","conclusion":"These results suggest that (i) silibinin is not resorbed by the chylomicron pathway, and (ii) the endogenous lipoprotein pathway VLDL → LDL may play a role in the transport of silibinin from the liver to the extrahepatic tissues concurrently facilitating the lipoprotein antioxidant influence of silibinin.","limitations":"small n (3-5) per group; radioactivity measured rather than parent compound in most data; some data figure-only; variance type not defined in Tables 1-2; olive oil doses not matched to human intake; anaesthetized rats"},"12885100":{"pmid":"12885100","title":"Coadministration of milk thistle and indinavir in healthy subjects.","authors":"DiCenzo R, Shelton M, Jordan K, Koval C, Forrest A, Reichman R, Morse G","journal":"Pharmacotherapy","year":"2003","volume":"23","issue":"7","pages":"866-70","doi":"10.1592/phco.23.7.866.32723","url":"https://pubmed.ncbi.nlm.nih.gov/12885100/","species":"human","speciesRaw":"human","design":"other (specify)","n":"10","status":"off-target analyte","statusNote":"Drug-interaction study: measured analyte is indinavir plasma PK with and without silymarin; silymarin/silybin concentrations were not measured. Indinavir data are recorded below for completeness","conclusion":"Silymarin has no apparent effect on indinavir plasma concentrations.","limitations":"small n (10); not powered for bioequivalence; silymarin blood concentrations not measured; single silymarin dose level; sequential (non-randomized) design"},"15666173":{"pmid":"15666173","title":"Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis.","authors":"Mills E, Wilson K, Clarke M, Foster B, Walker S, Rachlis B, DeGroot N, Montori VM, Gold W, Phillips E, Myers S, Gallicano K","journal":"European journal of clinical pharmacology","year":"2005","volume":"61","issue":"1","pages":"1-7","doi":"10.1007/s00228-004-0843-z","url":"https://pubmed.ncbi.nlm.nih.gov/15666173/","species":"human","speciesRaw":"human","design":"RCT","n":"16","status":"off-target analyte","statusNote":"Randomized controlled drug-interaction study of milk thistle on indinavir pharmacokinetics plus meta-analysis; measured analyte is indinavir, silymarin/silybin not measured. Indinavir data recorded for completeness","conclusion":"In our trial, we did not observe an interaction between milk thistle and indinavir.","limitations":"small sample size; open-label, no placebo; two control participants excluded; silymarin concentrations not measured; washout period possibly insufficient; healthy males only; control group indinavir AUC declined over time"},"16221754":{"pmid":"16221754","title":"Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans.","authors":"Gurley BJ, Barone GW, Williams DK, Carrier J, Breen P, Yates CR, Song PF, Hubbard MA, Tong Y, Cheboyina S","journal":"Drug metabolism and disposition: the biological fate of chemicals","year":"2006","volume":"34","issue":"1","pages":"69-74","doi":"10.1124/dmd.105.006312","url":"https://pubmed.ncbi.nlm.nih.gov/16221754/","species":"human","speciesRaw":"human","design":"open-label, randomized sequence, within-subject (each subject received all four interventions), pre/post","n":"16","status":"off-target analyte","statusNote":"Herb-drug interaction study: measured analyte is digoxin (P-gp substrate), not milk thistle flavanolignans (no silymarin/silibinin plasma levels measured). Digoxin PK extracted as recorded effect of milk thistle on a co-administered drug's absorption.","conclusion":"when compared with the effects of rifampin and clarithromycin, the botanical supplements milk thistle and black cohosh produced no significant changes in the disposition of digoxin, a clinically recognized P-gp substrate with a narrow therapeutic index.","limitations":"open-label; supplement flavanolignan plasma concentrations not measured; single product lot / formulation (soft gel contents appeared to remain undissolved); small n; haplotype subgroups very small; analyte is digoxin not milk thistle"},"16275123":{"pmid":"16275123","title":"Effect of silymarin and its polyphenolic fraction on cholesterol absorption in rats.","authors":"Sobolová L, Skottová N, Vecera R, Urbánek K","journal":"Pharmacological research","year":"2006","volume":"53","issue":"2","pages":"104-12","doi":"10.1016/j.phrs.2005.09.004","url":"https://pubmed.ncbi.nlm.nih.gov/16275123/","species":"rodent","speciesRaw":"rodent","design":"parallel-group animal experiment","n":"NR","status":"off-target analyte","statusNote":"Study of the effect of silymarin/polyphenolic fraction on intestinal absorption of dietary cholesterol in rats (dual-isotope method). Measured analyte is cholesterol, not silymarin; no silymarin/silibinin absorption or PK measured. Cholesterol absorption % is figure-only.","conclusion":"The major new finding in this study is that silymarin and its polyphenolic fraction inhibit cholesterol absorption in intestine of rats fed on high cholesterol diet and consequently positively modify lipoprotein cholesterol profile in plasma and content of lipids (cholesterol, TAG) in liver.","limitations":"cholesterol absorption values figure-only; n per group not given precisely (10-20); animal model; silymarin itself not measured; analyte is cholesterol not silymarin"},"16278402":{"pmid":"16278402","title":"Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan.","authors":"van Erp NP, Baker SD, Zhao M, Rudek MA, Guchelaar HJ, Nortier JW, Sparreboom A, Gelderblom H","journal":"Clinical cancer research : an official journal of the American Association for Cancer Research","year":"2005","volume":"11","issue":"21","pages":"7800-6","doi":"10.1158/1078-0432.CCR-05-1288","url":"https://pubmed.ncbi.nlm.nih.gov/16278402/","species":"human","speciesRaw":"human","design":"open-label, single-arm, sequential (within-patient: irinotecan alone then with milk thistle), not randomized, no placebo","n":"6","status":"complete","statusNote":"Primary outcome was irinotecan PK (off-target analyte, extracted too); silybin plasma steady-state concentrations (Table 4) are the on-target absorption data.","conclusion":"Silybin concentrations after intake of milk thistle are too low to significantly affect the function of CYP3A4 and UGT1A1 in vivo, indicating that milk thistle is unlikely to alter the disposition of anticancer drugs metabolized by these enzymes.","limitations":"n = 6; not randomized; no placebo control; silybin sampled only after irinotecan dosing (min/max over 48 h), no full silybin PK profile; ~10-fold interindividual variability in silybin concentrations; UGT1A1 genotype not assessed"},"16300915":{"pmid":"16300915","title":"The preparation of silybin-phospholipid complex and the study on its pharmacokinetics in rats.","authors":"Yanyu X, Yunmei S, Zhipeng C, Qineng P","journal":"International journal of pharmaceutics","year":"2006","volume":"307","issue":"1","pages":"77-82","doi":"10.1016/j.ijpharm.2005.10.001","url":"https://pubmed.ncbi.nlm.nih.gov/16300915/","species":"rodent","speciesRaw":"rodent","design":"randomized parallel (two groups) comparison, plus in vitro physicochemical tests","n":"12","status":"complete","statusNote":"","conclusion":"Drugs and phospholipids of phospholipids complex in vitro had not changed characteristics of themselves, but the combination changed greatly their characteristics in vivo, such as a remarkable enhancement of GI tract absorption.","limitations":"no variance reported for PK parameters; no statistical testing reported; small n (6 per group); AUC inconsistent between abstract and Table 3; no IV reference so absolute bioavailability not determined; sampling timepoints not listed in text"},"16356669":{"pmid":"16356669","title":"Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation.","authors":"El-Samaligy MS, Afifi NN, Mahmoud EA","journal":"International journal of pharmaceutics","year":"2006","volume":"308","issue":"1-2","pages":"140-8","doi":"10.1016/j.ijpharm.2005.11.006","url":"https://pubmed.ncbi.nlm.nih.gov/16356669/","species":"in_vitro","speciesRaw":"in vitro","design":"in vitro/ex vivo formulation experiments with 2^3 factorial designs","n":"NR","status":"partial","statusNote":"Formulation study of silymarin liposomes; absorption-related data are ex vivo chicken cheek pouch permeation (figure-only; only p-values in text). Encapsulation efficiency (%E) and in vitro release data are formulation parameters and not extracted as absorption values.","conclusion":"In vitro permeation study through chicken cheek pouch of hybrid liposomes containing L:Ch:SA:T 20 of 9:1:1:0.5 molar ratio showed superior permeation results compared with neutral or positively charged liposomes.","limitations":"ex vivo chicken pouch, no in vivo bioavailability measured despite title; permeation values figure-only; n = 3; dead tissue lacks endocytosis"},"16432272":{"pmid":"16432272","title":"Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin.","authors":"Gurley B, Hubbard MA, Williams DK, Thaden J, Tong Y, Gentry WB, Breen P, Carrier DJ, Cheboyina S","journal":"Journal of clinical pharmacology","year":"2006","volume":"46","issue":"2","pages":"201-13","doi":"10.1177/0091270005284854","url":"https://pubmed.ncbi.nlm.nih.gov/16432272/","species":"human","speciesRaw":"human","design":"open-label, randomized sequence, within-subject (each subject received all four interventions), pre/post","n":"19","status":"off-target analyte","statusNote":"Herb-drug interaction study: measured analyte is midazolam and its metabolite 1-hydroxymidazolam (CYP3A probe), not milk thistle flavanolignans (no silymarin serum concentrations measured). Midazolam PK extracted as the recorded effect of milk thistle on a co-administered drug.","conclusion":"when compared to the effects of rifampin and clarithromycin, the specific brand of milk thistle and black cohosh supplements used in this study produced no significant changes in the disposition of MDZ, a clinically recognized CYP3A substrate. Accordingly, these 2 products appear to pose no clinically significant risk for CYP3A-mediated herb-drug interactions.","limitations":"open-label; flavanolignan serum concentrations not measured; single product lot; softgel contents appeared to remain undissolved; results may not extend to higher doses, longer durations, or other formulations; analyte is midazolam not milk thistle"},"16527467":{"pmid":"16527467","title":"Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system.","authors":"Wu W, Wang Y, Que L","journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V","year":"2006","volume":"63","issue":"3","pages":"288-94","doi":"10.1016/j.ejpb.2005.12.005","url":"https://pubmed.ncbi.nlm.nih.gov/16527467/","species":"other_animal","speciesRaw":"other animal (rabbit)","design":"randomized crossover (SMEDDS vs PEG 400 solution, 6 rabbits, 7-day washout); separate preliminary evaluation of suspension in 6 rabbits","n":"NR","status":"complete","statusNote":"","conclusion":"Relative bioavailability of silymarin SMEDDS was dramatically enhanced, approximately 1.88- and 48.82-fold that of silymarin PEG 400 solution and suspension, respectively. It was concluded that alternative mechanisms other than improved release contribute to enhancement of bioavailability of silymarin.","limitations":"small n (6 rabbits); suspension compared in separate preliminary evaluation with no tabulated PK; very high dose (300 mg/kg); PEG 400 solution used as reference not a clinical formulation; text and table labelling of solution vs SMEDDS inconsistent"},"16687221":{"pmid":"16687221","title":"Preparation of silymarin proliposome: a new way to increase oral bioavailability of silymarin in beagle dogs.","authors":"Yan-yu X, Yun-mei S, Zhi-peng C, Qi-neng P","journal":"International journal of pharmaceutics","year":"2006","volume":"319","issue":"1-2","pages":"162-8","doi":"10.1016/j.ijpharm.2006.03.037","url":"https://pubmed.ncbi.nlm.nih.gov/16687221/","species":"other_animal","speciesRaw":"other animal (beagle dog)","design":"randomized parallel (two groups of 6)","n":"12","status":"complete","statusNote":"","conclusion":"Silymarin proliposome was stable and did enchance the gastrointestinal absorption of silymarin.","limitations":"small n (6 per group); no statistical comparison reported; variance type for ± not stated; AUC inconsistent between abstract/Table 3 and Table 2; control was silymarin capsule, not a solution; sampling to 12 h only"},"17077998":{"pmid":"17077998","title":"A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients.","authors":"Flaig TW, Gustafson DL, Su LJ, Zirrolli JA, Crighton F, Harrison GS, Pierson AS, Agarwal R, Glodé LM","journal":"Investigational new drugs","year":"2007","volume":"25","issue":"2","pages":"139-46","doi":"10.1007/s10637-006-9019-2","url":"https://pubmed.ncbi.nlm.nih.gov/17077998/","species":"human","speciesRaw":"human","design":"phase I dose-escalation, open-label, single-arm (intra-patient escalation allowed)","n":"13","status":"partial","statusNote":"Phase I dose-escalation study with PK of silibinin; plasma Cmax/AUC by dose level are figure-only (Figs. 2-3); only half-life range and urine concentrations are printed in text.","conclusion":"this study demonstrates the tolerability of high-dose, oral silybin-phytosome in patients with prostate cancer. The most significant toxicity observed was asymptomatic liver abnormalities, most notably unconjugated hyperbilirubinemia, with chronic administration. The recommended phase II oral dose of silybin-phytosome is 13 g daily, in 3 divided doses.","limitations":"PK values figure-only; prominent interpatient and intrapatient variability; small n per dose level; sparse sampling (to 4 h only); urine collection untimed"},"17315537":{"pmid":"17315537","title":"Development of a HPLC-UV assay for silybin-phosphatidylcholine complex (silybinin capsules) and its pharmacokinetic study in healthy male Chinese volunteers.","authors":"Li W, Gao J, Zhao HZ, Liu CX","journal":"European journal of drug metabolism and pharmacokinetics","year":"2006","volume":"31","issue":"4","pages":"265-70","doi":"10.1007/BF03190466","url":"https://pubmed.ncbi.nlm.nih.gov/17315537/","species":"human","speciesRaw":"human","design":"single-arm, open-label single-dose PK study","n":"20","status":"complete","statusNote":"","conclusion":"After administration of single oral doses of silybin-phosphatidylcholine complex (equivalent to 280mg silybin) to 20 subjects, Silybin was absorpted rapidly. The times to reach peak plasma concentration (Tmax) ranged from 0.67 to 2.67h, and the mean was 1.4h.","limitations":"single-arm, no comparator formulation; male subjects only; wide intersubject variability; CL and Vd not bioavailability-corrected (as printed, CL/Vd defined from dose/AUC); manufacturer-affiliated authors; poor text layer; values verified on page images"},"17328246":{"pmid":"17328246","title":"Formulation and biopharmaceutical evaluation of silymarin using SMEDDS.","authors":"Woo JS, Kim TS, Park JH, Chi SC","journal":"Archives of pharmacal research","year":"2007","volume":"30","issue":"1","pages":"82-9","doi":"10.1007/BF02977782","url":"https://pubmed.ncbi.nlm.nih.gov/17328246/","species":"rodent","speciesRaw":"rodent","design":"other (rat PK, test vs reference; design as printed not stated as crossover/parallel)","n":"NR","status":"complete","statusNote":"Silymarin SMEDDS vs Legalon capsule in rats (plus in vitro release); silybin measured in rat plasma after enzymatic deconjugation (total silybin).","conclusion":"After oral administration to rats, the SMEDDS containing silymarin had a 360% higher bioavailability compared with the reference capsule.","limitations":"rat study; n=7; variance type SE for PK; dose basis as silymarin; Tmax SE 0.00; release values figure-only"},"17348898":{"pmid":"17348898","title":"Bioavailability of a silybin-phosphatidylcholine complex in dogs.","authors":"Filburn CR, Kettenacker R, Griffin DW","journal":"Journal of veterinary pharmacology and therapeutics","year":"2007","volume":"30","issue":"2","pages":"132-8","doi":"10.1111/j.1365-2885.2007.00834.x","url":"https://pubmed.ncbi.nlm.nih.gov/17348898/","species":"other_animal","speciesRaw":"other animal (dog, beagle)","design":"other (parallel design with day-7 switch of test articles in group B; group A silymarin on day 7 after 6-day washout)","n":"16","status":"complete","statusNote":"Dog PK of silybin-phosphatidylcholine complex (SPC, Marin tablet) vs silymarin extract; total plasma silybin.","conclusion":"This study clearly shows that oral administration of silybin in a phosphatidylcholine complex (phytosome) results in greater bioavailability of silybin compared with standard silymarin extract.","limitations":"very high inter-animal variability (SD > mean for some); SPC tablet also contains zinc and vitamin E; different fasting duration day 0 vs day 7; emesis in group A after SPC on day 0, no PK data; sponsor-affiliated"},"17548790":{"pmid":"17548790","title":"Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies.","authors":"Kroll DJ, Shaw HS, Oberlies NH","journal":"Integrative cancer therapies","year":"2007","volume":"6","issue":"2","pages":"110-9","doi":"10.1177/1534735407301825","url":"https://pubmed.ncbi.nlm.nih.gov/17548790/","species":"unclear","speciesRaw":"NR","design":"NR","n":"NR","status":"review/non-primary","statusNote":"Narrative review of milk thistle nomenclature/chemistry and previously published pharmacokinetic studies (Kroll, Shaw, Oberlies, Integr Cancer Ther 2007); no original absorption data.","conclusion":"Precision in nomenclature, however, has lagged behind this progress. ... we urge clinicians and preclinical investigators alike to exercise rigor in nomenclature and use pure compounds or precisely defined chemical mixtures in subsequent studies.","limitations":"review article, secondary source"},"17692492":{"pmid":"17692492","title":"Analysis of silibinin in rat plasma and bile for hepatobiliary excretion and oral bioavailability application.","authors":"Wu JW, Lin LC, Hung SC, Chi CW, Tsai TH","journal":"Journal of pharmaceutical and biomedical analysis","year":"2007","volume":"45","issue":"4","pages":"635-41","doi":"10.1016/j.jpba.2007.06.026","url":"https://pubmed.ncbi.nlm.nih.gov/17692492/","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups i.v. vs oral; no crossover described)","n":"12","status":"complete","statusNote":"Analytical method paper that also reports rat PK of silibinin (i.v. 100 mg/kg vs oral 500 mg/kg) in plasma and bile; unconjugated and total (beta-glucuronidase) silibinin; silibinin = silybin A+B (milk thistle). Short communication.","conclusion":"After silibinin administration in rats, the disposition of silibinin in the plasma and bile fluid was due to rapid distribution and equilibration between the blood and hepatobiliary system, and the bile levels of unconjugated silibinin and total silibinin were greater than those in the plasma. The oral bioavailability of silibinin in rats was estimated to be 0.73%.","limitations":"rat study; very high doses (100 mg/kg i.v., 500 mg/kg oral); n=6; anesthetized i.v. group vs conscious oral group; bioavailability value inconsistent (0.73% vs 0.95%); Tmax unit not printed in Table 4; AUC units as printed 'min mg/mL'"},"17913795":{"pmid":"17913795","title":"Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract.","authors":"Wen Z, Dumas TE, Schrieber SJ, Hawke RL, Fried MW, Smith PC","journal":"Drug metabolism and disposition: the biological fate of chemicals","year":"2008","volume":"36","issue":"1","pages":"65-72","doi":"10.1124/dmd.107.017566","url":"https://pubmed.ncbi.nlm.nih.gov/17913795/","species":"human","speciesRaw":"human","design":"single-arm","n":"3","status":"complete","statusNote":"Human PK of free, conjugated and total silymarin flavonolignans after single 600 mg milk thistle extract; n=3. Also composition of commercial extracts (Table 1, not absorption data).","conclusion":"These data suggest that, after oral administration, silymarin flavonolignans are quickly metabolized to their conjugates, primarily forming glucuronides, and the conjugates are primary components present in human plasma.","limitations":"n=3 volunteers; no fed/fasted state or demographics stated; no IV reference so bioavailability not estimated; conjugates not individually quantified; conjugated = total minus free; Table 3 pooled plasma, mean of duplicates"},"18048488":{"pmid":"18048488","title":"Hepatobiliary excretion of silibinin in normal and liver cirrhotic rats.","authors":"Wu JW, Lin LC, Hung SC, Lin CH, Chi CW, Tsai TH","journal":"Drug metabolism and disposition: the biological fate of chemicals","year":"2008","volume":"36","issue":"3","pages":"589-96","doi":"10.1124/dmd.107.017004","url":"https://pubmed.ncbi.nlm.nih.gov/18048488/","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, five groups)","n":"NR","status":"complete","statusNote":"Rat PK of silibinin given intravenously (on-target compound, i.v. route; no oral arm): plasma and bile, unconjugated and total (beta-glucuronidase) silibinin; dose range, cyclosporin A interaction, DMN cirrhosis.","conclusion":"In the DMN-induced liver cirrhotic rats, the AUC of plasma unconjugated silibinin was reduced by 53%; however, total silibinin was increased by 182%. These results together suggest that the phase II conjugative reaction of silibinin was blocked by treatment with DNM.","limitations":"rat study, i.v. only (no oral absorption); anesthetized, bile-cannulated animals; n=6 per group; AUC interval NR; Abstract vs Results percentage inconsistencies"},"18054294":{"pmid":"18054294","title":"Preparative chromatographic purification of diastereomers of silybin and their quantification in human plasma by liquid chromatography-tandem mass spectrometry.","authors":"Li W, Han J, Li Z, Li X, Zhou S, Liu C","journal":"Journal of chromatography. B, Analytical technologies in the biomedical and life sciences","year":"2008","volume":"862","issue":"1-2","pages":"51-7","doi":"10.1016/j.jchromb.2007.10.040","url":"https://pubmed.ncbi.nlm.nih.gov/18054294/","species":"human","speciesRaw":"human","design":"single-arm","n":"22","status":"complete","statusNote":"Primarily an analytical method paper (prep-HPLC purification and LC-MS/MS assay of silybin A/B); includes human PK application (Table 3) after single oral silybin-phosphatidylcholine complex.","conclusion":"This research also outlines a simple, sensitive, selective and reproducible LC-MS-MS method that has been validated for the determination of both silybin A and silybin B in human plasma with a lower limit of quantitation of 2 ng/ml. The LC-MS-MS method described has been successfully applied to pharmacokinetic studies in healthy subjects.","limitations":"method paper; PK is an application; n=22 single-arm, no comparator; variance type for Table 3 not stated; sponsor-affiliated authors; unconjugated vs total silybin not specified"},"18428992":{"pmid":"18428992","title":"Solid state mechanochemical simultaneous activation of the constituents of the Silybum marianum phytocomplex with crosslinked polymers.","authors":"Voinovich D, Perissutti B, Magarotto L, Ceschia D, Guiotto P, Bilia AR","journal":"Journal of pharmaceutical sciences","year":"2009","volume":"98","issue":"1","pages":"215-28","doi":"10.1002/jps.21417","url":"https://pubmed.ncbi.nlm.nih.gov/18428992/","species":"rodent","speciesRaw":"rodent","design":"other (parallel, three formulations; composite curves)","n":"NR","status":"complete","statusNote":"Rat PK/in vitro dissolution of S. marianum dry extract vs coground systems with PVP-CL and Ac-Di-Sol; plasma silybin A, silybin B, silychristin (total after glucuronidase/arylsulfatase).","conclusion":"It can be concluded that the solid state mechanochemical process is a viable means to increase the in vitro solubilization of various active components and therefore to improve their bioavailability when given by oral route.","limitations":"very small rat study (four rats, per Methods); composite plasma curves, no variance; 4 time points only; dose-normalization to analyte dose differs between arms (8.5 vs 2.6 mg/kg); no statistics"},"18566043":{"pmid":"18566043","title":"The pharmacokinetics of silymarin is altered in patients with hepatitis C virus and nonalcoholic Fatty liver disease and correlates with plasma caspase-3/7 activity.","authors":"Schrieber SJ, Wen Z, Vourvahis M, Smith PC, Fried MW, Kashuba AD, Hawke RL","journal":"Drug metabolism and disposition: the biological fate of chemicals","year":"2008","volume":"36","issue":"9","pages":"1909-16","doi":"10.1124/dmd.107.019604","url":"https://pubmed.ncbi.nlm.nih.gov/18566043/","species":"human","speciesRaw":"human","design":"open-label, nonrandomized, parallel cohorts, single dose","n":"20","status":"complete","statusNote":"Single-dose PK of six silymarin flavonolignans (parent and total) in healthy volunteers vs HCV noncirrhotic, HCV cirrhotic and NAFLD patients (n=5 each).","conclusion":"These findings suggest that the pharmacokinetics of silymarin is altered in patients with liver disease. Patients with cirrhosis had the highest plasma caspase-3/7 activity and also achieved the highest exposures for the major silymarin flavonolignans.","limitations":"n=5 per cohort; healthy cohort about 20 years younger than patient cohorts; 24-h sampling insufficient for precise terminal phase; wide CIs, geometric means; dose stated as both 600 mg and 480 mg in text"},"19041708":{"pmid":"19041708","title":"Drug-drug interactions of silymarin on the perspective of pharmacokinetics.","authors":"Wu JW, Lin LC, Tsai TH","journal":"Journal of ethnopharmacology","year":"2009","volume":"121","issue":"2","pages":"185-93","doi":"10.1016/j.jep.2008.10.036","url":"https://pubmed.ncbi.nlm.nih.gov/19041708/","species":"unclear","speciesRaw":"NR","design":"NR","n":"NR","status":"review/non-primary","statusNote":"Review article (J Ethnopharmacol 2009) on pharmacokinetic drug-drug interactions of silymarin; no original absorption data. Page 1 (abstract, contents) read; article labelled 'Review'.","conclusion":"Silymarin has limited effect on the pharmacokinetics of several drugs in vivo; despite silymarin decreasing the activity of cytochrome P-450 (CYPs) enzymes, UDP-glucuronosyltransferase (UGT) enzyme, and reducing P-glycoprotein (P-gp) transport. Health-care practitioners should caution patients against co-administration of silymarin and pharmaceutical drugs.","limitations":"review article, secondary source"},"19226635":{"pmid":"19226635","title":"Solid state mechanochemical activation of Silybum marianum dry extract with betacyclodextrins: Characterization and bioavailability of the coground systems.","authors":"Voinovich D, Perissutti B, Grassi M, Passerini N, Bigotto A","journal":"Journal of pharmaceutical sciences","year":"2009","volume":"98","issue":"11","pages":"4119-29","doi":"10.1002/jps.21704","url":"https://pubmed.ncbi.nlm.nih.gov/19226635/","species":"rodent","speciesRaw":"rodent","design":"other (parallel, two formulations, pilot study, composite plasma curves)","n":"NR","status":"complete","statusNote":"Rat PK pilot (n=4 per formulation, composite curves) plus in vitro dissolution and solid-state characterization of milk thistle dry extract co-ground with beta-cyclodextrin vs commercial product.","conclusion":"Finally, the in vivo absorption studies in rats revealed a very remarkable improvement of the oral bioavailability of the dry extract with respect to the reference product.","limitations":"pilot study, no formal statistical test; n=4 rats per formulation; PK from composite plasma curves (no per-animal variance); only three sampling times (1, 2, 4 h); no variance reported; single dose level"},"19470289":{"pmid":"19470289","title":"Pharmacokinetic interaction between oltipraz and silymarin in rats.","authors":"Kang MK, Bae SK, Kim JW, Lee MG","journal":"Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques","year":"2009","volume":"12","issue":"1","pages":"1-16","doi":"10.18433/j38c7w","url":"https://pubmed.ncbi.nlm.nih.gov/19470289/","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, drug-drug interaction PK study in rats)","n":"NR","status":"complete","statusNote":"Rat PK interaction study; silibinin (from silymarin) PK values extracted; oltipraz PK values (Tables 1, 3, 5) not extracted as oltipraz is not the listed supplement.","conclusion":"After single intravenous administration of the drugs together, the AUC of unconjugated silibinin was significantly smaller, but that of both conjugated and total silibinin was significantly greater. This could have been due to an increase in the formation of conjugates (glucuronidation and sulfation) of silibinin as induced by oltipraz. After simultaneous oral administration of the drugs, however, the AUCs (or AUC0−12 h) of unconjugated, conjugated, and total silibinin were comparable.","limitations":"rat study; extrapolation to humans not tested; drug-interaction design; fasting state not stated; large SDs, means of individual rat parameters; oltipraz PK values not extracted"},"19841158":{"pmid":"19841158","title":"Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C.","authors":"Hawke RL, Schrieber SJ, Soule TA, Wen Z, Smith PC, Reddy KR, Wahed AS, Belle SH, Afdhal NH, Navarro VJ, Berman J, Liu QY, Doo E, Fried MW","journal":"Journal of clinical pharmacology","year":"2010","volume":"50","issue":"4","pages":"434-49","doi":"10.1177/0091270009347475","url":"https://pubmed.ncbi.nlm.nih.gov/19841158/","species":"human","speciesRaw":"human","design":"other (double-masked, placebo-controlled, sequential ascending multiple-dose phase I; 3:1 randomization)","n":"32 randomized (4 cohorts of 8); PK n=6 per active cohort (560 mg cohort n=5)","status":"complete","statusNote":"Phase I ascending multiple-dose PK in noncirrhotic HCV patients; single-dose PK reported separately in another paper.","conclusion":"Oral doses of silymarin up to 2.1 g per day were safe and well tolerated. The nonlinear pharmacokinetics of silybin A and silybin B suggests low bioavailability associated with customary doses of silymarin may be overcome with doses above 700 mg.","limitations":"small n per cohort (6 active); patients with HCV, not generalizable to healthy or other liver disease populations; sequential non-randomized dose cohorts; medians and ranges, many parent values not detectable at low doses; industry-supplied product and partial funding"},"19863195":{"pmid":"19863195","title":"Self-assembly and characterization of Pluronic P105 micelles for liver-targeted delivery of silybin.","authors":"Li X, Huang Y, Chen X, Zhou Y, Zhang Y, Li P, Liu Y, Sun Y, Zhao J, Wang F","journal":"Journal of drug targeting","year":"2009","volume":"17","issue":"10","pages":"739-50","doi":"10.3109/10611860903062062","url":"https://pubmed.ncbi.nlm.nih.gov/19863195/","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, two micelle formulations, IV)","n":"NR","status":"complete","statusNote":"IV rat PK and tissue distribution of silybin in micelles (route IV, on-target); no oral absorption data. Micelle characterization and CMC also reported.","conclusion":"LA-P105 has been successfully synthesized and utilized to self-assemble micelles to encapsulate a highly hydrophobic drug, silybin. [...] biodistribution studies confirmed that selective targeting of silybin-loaded LA-P105 micelles into liver occurred in a site-specific manner. In conclusion, LA-P105 is a promising polymer for preparing liver-targeting polymeric micelles.","limitations":"intravenous administration only, no oral absorption; n=3 per group; tissue concentration data figure-only; no sampling times listed in text; micelle formulation, not a dietary supplement form"},"20332565":{"pmid":"20332565","title":"In vitro and in vivo evaluation of silybin nanosuspensions for oral and intravenous delivery.","authors":"Wang Y, Zhang D, Liu Z, Liu G, Duan C, Jia L, Feng F, Zhang X, Shi Y, Zhang Q","journal":"Nanotechnology","year":"2010","volume":"21","issue":"15","pages":"155104","doi":"10.1088/0957-4484/21/15/155104","url":"https://pubmed.ncbi.nlm.nih.gov/20332565/","species":"in_vitro","speciesRaw":"other animal (beagle dog); in vitro Caco-2","design":"other (parallel groups, formulation comparison; oral and IV)","n":"18","status":"complete","statusNote":"Oral and IV silybin nanosuspension PK in beagle dogs (n=3 per group), plus in vitro dissolution and Caco-2 permeability.","conclusion":"In accordance with the in vitro drug releasing data and the transport values, the pharmacokinetics study clearly demonstrated that decreasing the particle size of the nanosuspensions could achieve higher oral bioavailability. However, for controlled drug delivery, it is proposed to use the slightly larger particle nanosuspension for IV administration","limitations":"n=3 dogs per group; variance type not stated; no statistical p-values printed for PK comparisons; parameter statistic types not stated; formulation study, not a dietary supplement; dose basis assumed as silybin active compound (stated as silybin dose)"},"20405254":{"pmid":"20405254","title":"Development of silymarin self-microemulsifying drug delivery system with enhanced oral bioavailability.","authors":"Li X, Yuan Q, Huang Y, Zhou Y, Liu Y","journal":"AAPS PharmSciTech","year":"2010","volume":"11","issue":"2","pages":"672-8","doi":"10.1208/s12249-010-9432-x","url":"https://pubmed.ncbi.nlm.nih.gov/20405254/","species":"other_animal","speciesRaw":"other animal (mongrel dog)","design":"randomized crossover","n":"6","status":"complete","statusNote":"Dog crossover PK of silymarin SMEDDS vs Legalon capsule (n=6) with in vitro release/solubility.","conclusion":"In in vivo studies for clinical purpose, SMEDDS showed significantly enhanced absorption than Legalon®.","limitations":"n=6 dogs; fasted state only; sampling times not listed; formulation study; dose basis for silymarin not specified beyond 50 mg/kg silymarin"},"20523105":{"pmid":"20523105","title":"Effects of silibinin, inhibitor of CYP3A4 and P-glycoprotein in vitro, on the pharmacokinetics of paclitaxel after oral and intravenous administration in rats.","authors":"Lee CK, Choi JS","journal":"Pharmacology","year":"2010","volume":"85","issue":"6","pages":"350-6","doi":"10.1159/000312690","url":"https://pubmed.ncbi.nlm.nih.gov/20523105/","species":"rodent","speciesRaw":"rodent","design":"parallel (7 groups of 6 rats); drug-interaction study","n":"42 (7 groups of 6 as printed)","status":"off-target analyte","statusNote":"PK study of paclitaxel (oral and IV) in rats with oral silibinin as pretreatment; silibinin plasma levels were not measured. Paclitaxel PK values not extracted.","conclusion":"Accordingly, the enhanced oral bioavailability in the presence of silibinin could mainly be due to the increased intestinal absorption of paclitaxel via P-gp inhibition.","limitations":"silibinin concentrations not measured; analyte is paclitaxel; rat model"},"20523347":{"pmid":"20523347","title":"Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles.","authors":"Yu JN, Zhu Y, Wang L, Peng M, Tong SS, Cao X, Qiu H, Xu XM","journal":"Acta pharmacologica Sinica","year":"2010","volume":"31","issue":"6","pages":"759-64","doi":"10.1038/aps.2010.55","url":"https://pubmed.ncbi.nlm.nih.gov/20523347/","species":"other_animal","speciesRaw":"other animal (dog)","design":"randomized crossover (described as three-way crossover with two formulations; 2 weeks washout)","n":"6","status":"complete","statusNote":"Dog PK (n=6) of silybin mixed micelles vs silybin-N-methylglucamine; compartmental parameters only, no per-group variance in table.","conclusion":"Sodium cholate/phospholipid-mixed micelles are promising carriers in orally delivery of silybin, considering their capability of enhancing bioavailability and large-scale production.","limitations":"n=6 dogs; no variance or p values for PK parameters in table; one-compartment fit despite double peaks; reference is soluble derivative silybin-N-methylglucamine, not a marketed capsule; text/table inconsistency in Cmax"},"20621458":{"pmid":"20621458","title":"Nanostructured lipid carriers for parenteral delivery of silybin: Biodistribution and pharmacokinetic studies.","authors":"Jia L, Zhang D, Li Z, Duan C, Wang Y, Feng F, Wang F, Liu Y, Zhang Q","journal":"Colloids and surfaces. B, Biointerfaces","year":"2010","volume":"80","issue":"2","pages":"213-8","doi":"10.1016/j.colsurfb.2010.06.008","url":"https://pubmed.ncbi.nlm.nih.gov/20621458/","species":"other_animal","speciesRaw":"other animal (New Zealand rabbit; Kunming mouse)","design":"other (parallel two-group, IV formulation comparison)","n":"8 rabbits; mice NR total","status":"complete","statusNote":"IV-only study (rabbit PK, mouse biodistribution) of silybin NLC vs solution; on-target compound, route IV; no oral absorption.","conclusion":"These results indicate that NLC is a potential sustained release and targeting system for silybin.","limitations":"intravenous only; n=4 per group; variance not in tables; multi-peak profiles; non-compartmental statistical moment analysis"},"20828605":{"pmid":"20828605","title":"Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities.","authors":"Doehmer J, Weiss G, McGregor GP, Appel K","journal":"Toxicology in vitro : an international journal published in association with BIBRA","year":"2011","volume":"25","issue":"1","pages":"21-7","doi":"10.1016/j.tiv.2010.09.001","url":"https://pubmed.ncbi.nlm.nih.gov/20828605/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro enzyme kinetics)","n":"NR","status":"not absorption-related","statusNote":"In vitro CYP inhibition/induction and hepatocyte cytotoxicity study of a milk thistle dry extract (HEPAR-PASCO) in human hepatocytes and liver microsomes. No absorption or PK measurements; plasma Cmax values (1.4 and 1.15 ug/ml silibinin) are cited from other literature, not measured.","conclusion":"According to FDA regulations 1 > cmax/Ki > 0.1 indicates, that drug-drug interactions are possible for CYPs 2C8, and 2C9, but not likely, and are remote for CYPs 2C19, 2D6, and 3A4.","limitations":"in vitro only; no absorption data"},"20942611":{"pmid":"20942611","title":"Polyamidoamine dendrimers as potential drug carriers for enhanced aqueous solubility and oral bioavailability of silybin.","authors":"Huang X, Wu Z, Gao W, Chen Q, Yu B","journal":"Drug development and industrial pharmacy","year":"2011","volume":"37","issue":"4","pages":"419-27","doi":"10.3109/03639045.2010.518150","url":"https://pubmed.ncbi.nlm.nih.gov/20942611/","species":"rodent","speciesRaw":"rodent","design":"randomized two-period crossover (rats)","n":"12","status":"complete","statusNote":"Rat crossover PK of silybin-PAMAM G2 complex vs silybin suspension; plus in vitro solubility and release (figure-only).","conclusion":"Complex of silybin with dendrimers led to sustained release of the drug in vitro and improved bioavailability in vivo.","limitations":"rat study, not human; variance type (SD/SEM) not stated; sampling timepoints not stated in text; solubility and release data figure-only; dose basis (silybin purity) not stated; funded by government grant; conflicts of interest not otherwise stated"},"21031623":{"pmid":"21031623","title":"Effect of silymarin administration on TNF-α serum concentration in peritoneal dialysis patients.","authors":"Nazemian F, Karimi G, Moatamedi M, Charkazi S, Shamsara J, Mohammadpour AH","journal":"Phytotherapy research : PTR","year":"2010","volume":"24","issue":"11","pages":"1654-7","doi":"10.1002/ptr.3175","url":"https://pubmed.ncbi.nlm.nih.gov/21031623/","species":"human","speciesRaw":"human","design":"single-arm","n":"15","status":"not absorption-related","statusNote":"Pharmacodynamic/efficacy study of silymarin on serum TNF-alpha and haemoglobin in peritoneal dialysis patients; no silymarin/silybin concentrations, PK or absorption parameters measured.","conclusion":"Based on the results of this study, it is suggested that silymarin may be useful in the treatment of inflammation for peritoneal dialysis patients.","limitations":"no absorption/PK data; single arm, n=15; not absorption-related"},"21111585":{"pmid":"21111585","title":"Oral bioavailability of silymarin phytocomplex formulated as self-emulsifying pellets.","authors":"Iosio T, Voinovich D, Perissutti B, Serdoz F, Hasa D, Grabnar I, Acqua SD, Zara GP, Muntoni E, Pinto JF","journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology","year":"2011","volume":"18","issue":"6","pages":"505-12","doi":"10.1016/j.phymed.2010.10.012","url":"https://pubmed.ncbi.nlm.nih.gov/21111585/","species":"rodent","speciesRaw":"rodent","design":"parallel (two groups of rats)","n":"8","status":"complete","statusNote":"Rat duodenal-administration PK of silymarin self-emulsifying pellets vs dry extract (plasma and lymph); formulation development data not extracted.","conclusion":"These preliminary technological and pharmacokinetic data demonstrated that extrusion/spheronisation is a viable technology to produce self-emulsifying pellets of good quality and able to improve in vivo oral bioavailability of main components of a phytotherapeutic extract of more than 100 times by enhancing the lymphatic route of absorption.","limitations":"n=4 per group; rats, duodenal dosing under anesthesia (bypasses stomach), not oral gavage; no statistical tests reported; doses of silybin A and B differ between arms; fold bioavailability stated in text only; plasma concentration profiles figure-only"},"21315924":{"pmid":"21315924","title":"Stripping voltammetric determination of silymarin in formulations and human blood utilizing bare and modified carbon paste electrodes.","authors":"El-Desoky HS, Ghoneim MM","journal":"Talanta","year":"2011","volume":"84","issue":"1","pages":"223-34","doi":"10.1016/j.talanta.2011.01.027","url":"https://pubmed.ncbi.nlm.nih.gov/21315924/","species":"human","speciesRaw":"human","design":"single-arm","n":"4","status":"complete","statusNote":"Primarily an analytical (voltammetry) method paper; human PK of silymarin (Table 5) from 4 volunteers in two groups of two is the only absorption content. Assay validation data (calibration, recovery, LOD/LOQ) not extracted.","conclusion":"The pharmacokinetic parameters of silymarin in plasma of healthy human volunteers were estimated following the administration of a single oral dose of 120 mg silymarin utilizing the modified carbon paste electrode. The estimated pharmacokinetic parameters were favorably compared with those reported in literature.","limitations":"n=4 (two groups of two); analytical method paper, PK is secondary; no variance reported; single-dose, co-formulated with vitamin E; silymarin measured as total electro-oxidisable SMR; metabolites (conjugates) reported as not oxidisable; dose basis unclear"},"21549187":{"pmid":"21549187","title":"Oil based nanocarrier for improved oral delivery of silymarin: In vitro and in vivo studies.","authors":"Parveen R, Baboota S, Ali J, Ahuja A, Vasudev SS, Ahmad S","journal":"International journal of pharmaceutics","year":"2011","volume":"413","issue":"1-2","pages":"245-53","doi":"10.1016/j.ijpharm.2011.04.041","url":"https://pubmed.ncbi.nlm.nih.gov/21549187/","species":"rodent","speciesRaw":"rodent","design":"parallel (three groups of six rats)","n":"18","status":"complete","statusNote":"Rat oral PK of silymarin nanoemulsion vs marketed suspension vs bulk drug suspension; in vitro release and hepatoprotective efficacy (CCl4) not extracted except release maximum.","conclusion":"The AUC and Cmax of TF14 formulation after oral administration were 4-fold and 6-fold higher than those of drug suspension of silymarin, respectively.","limitations":"rat study; n=6 per group; PK dose not stated in PK methods; fed/fasted state of PK animals not stated; AUC p-values not stated; large SD for marketed AUC"},"21656362":{"pmid":"21656362","title":"Effects of silymarin nanoemulsion against carbon tetrachloride-induced hepatic damage.","authors":"Parveen R, Baboota S, Ali J, Ahuja A, Vasudev SS, Ahmad S","journal":"Archives of pharmacal research","year":"2011","volume":"34","issue":"5","pages":"767-74","doi":"10.1007/s12272-011-0510-8","url":"https://pubmed.ncbi.nlm.nih.gov/21656362/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"30","status":"not absorption-related","statusNote":"Hepatoprotective efficacy of silymarin nanoemulsion vs standard silymarin suspension against CCl4 hepatotoxicity in rats (serum enzymes, tissue GSH/TBARS, histology). No plasma/tissue silymarin concentrations, PK or absorption data reported.","conclusion":"The results indicate an excellent potential of the nanoemulsion formulation for the reversal of CCl4-induced liver toxicity in rats as compared to standard silymarin.","limitations":"no absorption/PK data; efficacy study only"},"21666703":{"pmid":"21666703","title":"Proliposomes for oral delivery of dehydrosilymarin: preparation and evaluation in vitro and in vivo.","authors":"Chu C, Tong SS, Xu Y, Wang L, Fu M, Ge YR, Yu JN, Xu XM","journal":"Acta pharmacologica Sinica","year":"2011","volume":"32","issue":"7","pages":"973-80","doi":"10.1038/aps.2011.25","url":"https://pubmed.ncbi.nlm.nih.gov/21666703/","species":"other_animal","speciesRaw":"other animal (rabbit)","design":"parallel","n":"6","status":"off-target analyte","statusNote":"PK/absorption of dehydrosilymarin (a synthetic oxidized derivative of silymarin) measured as dehydrosilybin in rabbit plasma; not silymarin itself (authors could not detect drug after silymarin at the same dose). Data extracted for reference.","conclusion":"Proliposomes may be a useful vehicle for oral delivery of dehydrosilymarin, a drug poorly soluble in water.","limitations":"rabbit study, n=3 per group; off-target compound (dehydrosilymarin, not silymarin); no statistical tests reported for PK; Cmax only approximate in text, not in Table 2; LLOQ recovery 117-123% reported in Table 1 (method accuracy); no variance for tmax"},"21802925":{"pmid":"21802925","title":"A new approach to enhance oral bioavailability of Silybum Marianum dry extract: association of mechanochemical activation and spray congealing.","authors":"Passerini N, Perissutti B, Albertini B, Franceschinis E, Lenaz D, Hasa D, Locatelli I, Voinovich D","journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology","year":"2012","volume":"19","issue":"2","pages":"160-8","doi":"10.1016/j.phymed.2011.06.027","url":"https://pubmed.ncbi.nlm.nih.gov/21802925/","species":"rodent","speciesRaw":"rodent","design":"parallel (three groups of five rats)","n":"15","status":"complete","statusNote":"Rat PK pilot (n=5 per group) of Silybum marianum dry extract vs two spray-congealed microparticle formulations (M1, M3); characterisation data not extracted.","conclusion":"These microparticles promoted an excellent oral bioavailability in rats of the principal flavolignans of Silybum Marianum dry extract (silybin A and B) thanks to the stable activated solid state of the coground with Ac-Di-Sol and to the efficient dispersion in the amphiphilic Gelucire 50/13.","limitations":"pilot study, n=5 per group; rats only; no statistical tests reported; extremely low dry-extract Cmax values; industry-donated materials; Cmax/AUC given in ng/ml for 145 mg/kg dose, as printed"},"21865319":{"pmid":"21865319","title":"Differences in the disposition of silymarin between patients with nonalcoholic fatty liver disease and chronic hepatitis C.","authors":"Schrieber SJ, Hawke RL, Wen Z, Smith PC, Reddy KR, Wahed AS, Belle SH, Afdhal NH, Navarro VJ, Meyers CM, Doo E, Fried MW","journal":"Drug metabolism and disposition: the biological fate of chemicals","year":"2011","volume":"39","issue":"12","pages":"2182-90","doi":"10.1124/dmd.111.040212","url":"https://pubmed.ncbi.nlm.nih.gov/21865319/","species":"human","speciesRaw":"human","design":"RCT (double-blind, placebo-controlled phase 1 dose-escalation; PK reported for silymarin recipients)","n":"40 enrolled (8 per cohort); PK data n=6 per cohort (HCV 560 mg steady-state n=5)","status":"complete","statusNote":"","conclusion":"In summary, the efficacy of silymarin may be more readily observed in NAFLD patients because of their higher flavonolignan plasma concentrations and more extensive enterohepatic cycling compared with those in HCV patients.","limitations":"small cohorts (n=6 per cohort, some cells n=4-5); wide confidence intervals including negative bounds; only two dose levels; HCV 280 mg cohort from two cohorts; industry-supplied product and partial funding; no healthy control group in this paper; dose/weight differences between cohorts"},"21948306":{"pmid":"21948306","title":"Silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices: physical characterization and enhanced oral bioavailability.","authors":"Lian R, Lu Y, Qi J, Tan Y, Niu M, Guan P, Hu F, Wu W","journal":"AAPS PharmSciTech","year":"2011","volume":"12","issue":"4","pages":"1234-40","doi":"10.1208/s12249-011-9666-2","url":"https://pubmed.ncbi.nlm.nih.gov/21948306/","species":"other_animal","speciesRaw":"other animal (beagle dog)","design":"randomized crossover (three-period, three formulations)","n":"6","status":"complete","statusNote":"","conclusion":"Pharmacokinetic study showed significantly increased peak concentration for silymarin GMO/P407 LCM, and, most importantly, a 3.5-fold increase in silymarin oral bioavailability as compared with Legalon, a commercial silymarin formulation.","limitations":"n=6 dogs; no washout stated; variance type not stated in Table I; silymarin measured as silybin only; no statistical comment on relative bioavailability values; Legalon AUC0-inf exceeds AUC0-t by 2.6-fold with t1/2 3.69 h"},"22172604":{"pmid":"22172604","title":"Effects of silymarin and formulation on the oral bioavailability of paclitaxel in rats.","authors":"Park JH, Park JH, Hur HJ, Woo JS, Lee HJ","journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences","year":"2012","volume":"45","issue":"3","pages":"296-301","doi":"10.1016/j.ejps.2011.11.021","url":"https://pubmed.ncbi.nlm.nih.gov/22172604/","species":"rodent","speciesRaw":"rodent","design":"parallel groups (8 groups), n=5 per group","n":"NR","status":"off-target analyte","statusNote":"PK study measured plasma paclitaxel (a drug) in rats; silymarin was given only as a P-gp inhibitor co-administered orally and silymarin/silibinin itself was not measured. Data sections skipped.","conclusion":"silymarin is effective at enhancing the oral bioavailability of paclitaxel, a P-gp substrate, by inhibition of the P-gp efflux pump present in the epithelial cells of intestine.","limitations":"analyte is paclitaxel, not silymarin; silymarin concentrations not measured"},"22343518":{"pmid":"22343518","title":"Oral bioavailability of silymarin formulated as a novel 3-day delivery system based on porous silica nanoparticles.","authors":"Cao X, Fu M, Wang L, Liu H, Deng W, Qu R, Su W, Wei Y, Xu X, Yu J","journal":"Acta biomaterialia","year":"2012","volume":"8","issue":"6","pages":"2104-12","doi":"10.1016/j.actbio.2012.02.011","url":"https://pubmed.ncbi.nlm.nih.gov/22343518/","species":"in_vitro","speciesRaw":"other animal (beagle dog); in vitro release also","design":"parallel (4 groups)","n":"NR","status":"complete","statusNote":"","conclusion":"The prepared 3-day release formulation gave an initial burst release from SD, and a sustained release due to the PSNs. The smooth and stable connection of the two actions were attributed to the hydrophilic gel matrix, which showed a considerable increase in bioavailability compared to commercial tablets.","limitations":"small n (6 per group); variance, statistic type and AUC interval not reported for in vivo parameters; no p-values reported; industry-independent academic funding; dose basis NR; values for t1/2/AUC of arms A and B not tabulated; in vivo values partly figure-only"},"22530301":{"pmid":"22530301","title":"Enhancement of the in-vitro dissolution and in-vivo oral bioavailability of silymarin from liquid-filled hard gelatin capsules of semisolid dispersion using Gelucire 44/14 as a carrier.","authors":"Hussein A, El-Menshawe S, Afouna M","journal":"Die Pharmazie","year":"2012","volume":"67","issue":"3","pages":"209-14","doi":"NR","url":"https://pubmed.ncbi.nlm.nih.gov/22530301/","species":"in_vitro","speciesRaw":"other animal (New Zealand albino rabbit); in vitro dissolution also","design":"parallel (3 groups, randomly classified)","n":"18","status":"complete","statusNote":"","conclusion":"SD of silymarin with Gelucire 44/14 had a pronounced effect on the drug solubility, in vitro dissolution rates and bioavailability. Further, the relative bioavailability of silymarin SD with Gelucire 44/14 test formulation was superior to that of reference standard (commercial product; Hepaticum).","limitations":"n per group not stated (18 rabbits in 3 groups); dose basis unclear (silymarin vs silybin); plasma Cmax unit printed µg/ml and AUC unit printed g.h/ml (silybin plasma levels of this magnitude look implausible; units as printed); variance type given in text as S.E. but p-values not reported; statistical text internally inconsistent (p > 0.05 called significant); sparse sampling (7 timepoints)"},"23067546":{"pmid":"23067546","title":"Silymarin attenuates benzo(a)pyrene induced toxicity by mitigating ROS production, DNA damage and calcium mediated apoptosis in peripheral blood mononuclear cells (PBMC).","authors":"Perumal Vijayaraman K, Muruganantham S, Subramanian M, Shunmugiah KP, Kasi PD","journal":"Ecotoxicology and environmental safety","year":"2012","volume":"86","issue":"","pages":"79-85","doi":"10.1016/j.ecoenv.2012.08.031","url":"https://pubmed.ncbi.nlm.nih.gov/23067546/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro cell treatment, triplicates)","n":"NR","status":"not absorption-related","statusNote":"In vitro toxicology study of silymarin (2.4 mg/ml) protecting human PBMC against benzo(a)pyrene (ROS, DNA damage, apoptosis, intracellular calcium, CYP1A1/1B1 activity). No absorption or pharmacokinetic measurements. Data sections skipped.","conclusion":"This multifaceted compound has a very good potential in suppressing the effect of B(a)P in PBMC, by at least more than one mechanism.","limitations":"no absorption or PK data"},"23072776":{"pmid":"23072776","title":"Absorption and metabolism of milk thistle flavanolignans in humans.","authors":"Calani L, Brighenti F, Bruni R, Del Rio D","journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology","year":"2012","volume":"20","issue":"1","pages":"40-6","doi":"10.1016/j.phymed.2012.09.004","url":"https://pubmed.ncbi.nlm.nih.gov/23072776/","species":"human","speciesRaw":"human","design":"single-arm","n":"15","status":"complete","statusNote":"","conclusion":"milk thistle flavonolignans are extensively modified after ingestion and recovered in urine as sulpho- and glucuronyl-conjugates, indicating a strong affinity for hepatic phase II enzymes.","limitations":"urine only, no plasma PK; bioavailability estimated from urinary recovery; conjugates quantified with quercetin-glucuronide as surrogate standard; single-arm, no comparator; dose given as formulation weight; dose basis in text ambiguous (380 mg silymarin extract vs 484.5 µmol flavonolignans); microbial catabolites not assessed"},"23205514":{"pmid":"23205514","title":"Effects of single or repeated silymarin administration on pharmacokinetics of risperidone and its major metabolite, 9-hydroxyrisperidone in rats.","authors":"Lee KS, Chae SW, Park JH, Park JH, Choi JM, Rhie SJ, Lee HJ","journal":"Xenobiotica; the fate of foreign compounds in biological systems","year":"2013","volume":"43","issue":"3","pages":"303-10","doi":"10.3109/00498254.2012.731092","url":"https://pubmed.ncbi.nlm.nih.gov/23205514/","species":"rodent","speciesRaw":"rodent","design":"parallel (7 groups)","n":"NR","status":"off-target analyte","statusNote":"Rat PK study measuring plasma risperidone and 9-hydroxyrisperidone; silymarin (40 mg/kg, single or repeated 5 days) was given only as a P-gp inhibitor and silymarin itself was not measured. Data sections skipped.","conclusion":"The repeated exposures of silymarin, compared to single administration of silymarin, increased oral bioavailability and affected the pharmacokinetics of risperidone and 9-hydroxyrisperidone, by inhibiting P-gp.","limitations":"analyte is risperidone, not silymarin; silymarin concentrations not measured"},"23401473":{"pmid":"23401473","title":"Interaction of silymarin flavonolignans with organic anion-transporting polypeptides.","authors":"Köck K, Xie Y, Hawke RL, Oberlies NH, Brouwer KL","journal":"Drug metabolism and disposition: the biological fate of chemicals","year":"2013","volume":"41","issue":"5","pages":"958-65","doi":"10.1124/dmd.112.048272","url":"https://pubmed.ncbi.nlm.nih.gov/23401473/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro transport inhibition)","n":"NR","status":"not absorption-related","statusNote":"In vitro OATP transporter inhibition study (IC50 of silymarin flavonolignans on OATP1B1/1B3/2B1-mediated uptake of E217G, E1S and rosuvastatin in cell lines and human hepatocytes). Measured analytes are radiolabelled probe substrates; no absorption/PK of silymarin measured. Table 3 portal vein concentrations are authors' calculations from literature Cmax (Hawke 2010) and rat Fa, not measured here. Data sections skipped.","conclusion":"The extent of silymarin-drug interactions depends on OATP isoform specificity and concentrations of flavonolignans at the site of drug transport. Higher than customary doses of silymarin, or formulations with improved bioavailability, may increase the risk of flavonolignan interactions with OATP substrates in patients.","limitations":"no absorption/PK measurement of silymarin"},"23835761":{"pmid":"23835761","title":"An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study.","authors":"Zhu HJ, Brinda BJ, Chavin KD, Bernstein HJ, Patrick KS, Markowitz JS","journal":"Drug metabolism and disposition: the biological fate of chemicals","year":"2013","volume":"41","issue":"9","pages":"1679-85","doi":"10.1124/dmd.113.052423","url":"https://pubmed.ncbi.nlm.nih.gov/23835761/","species":"human","speciesRaw":"human","design":"open-label dose escalation (single doses of 1, 2, 3 capsules on three occasions, then 28-day repeated dosing)","n":"14","status":"complete","statusNote":"","conclusion":"Pharmacokinetic analysis indicated that, in general, silymarin flavonolignans were rapidly absorbed and eliminated with short t1/2 after oral administration of a standardized extract.","limitations":"small n (13); free (unconjugated) flavonolignans only; conjugates not measured; many parameters not determined (below LLOQ) at lower doses; single product (Legalon 140); no p-values reported for CL/F comparisons"},"23851081":{"pmid":"23851081","title":"Silymarin loaded liposomes for hepatic targeting: in vitro evaluation and HepG2 drug uptake.","authors":"Elmowafy M, Viitala T, Ibrahim HM, Abu-Elyazid SK, Samy A, Kassem A, Yliperttula M","journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences","year":"2013","volume":"50","issue":"2","pages":"161-71","doi":"10.1016/j.ejps.2013.06.012","url":"https://pubmed.ncbi.nlm.nih.gov/23851081/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation characterization)","n":"NR","status":"partial","statusNote":"In vitro liposome formulation study (parenteral targeting); on-target (silymarin) in vitro data only: HepG2 cellular uptake, encapsulation efficiency, release kinetics. No in vivo PK (a rat pilot is mentioned as 'results not shown').","conclusion":"Cellular uptake studies with HepG2 cells demonstrated that Sito-G containing liposomes are potential drug carriers for silymarin to hepatic cells, and that there is an optimum amount of Sito-G needed for maximizing the HepG2 cell uptake of silymarin which was dependent on the liposome composition.","limitations":"in vitro only (HepG2); parenteral targeting formulation, not an oral absorption study; uptake percent basis not defined; F1 uptake figure only; in vivo rat pilot data not shown"},"24008629":{"pmid":"24008629","title":"Binary lipids-based nanostructured lipid carriers for improved oral bioavailability of silymarin.","authors":"Shangguan M, Lu Y, Qi J, Han J, Tian Z, Xie Y, Hu F, Yuan H, Wu W","journal":"Journal of biomaterials applications","year":"2014","volume":"28","issue":"6","pages":"887-96","doi":"10.1177/0885328213485141","url":"https://pubmed.ncbi.nlm.nih.gov/24008629/","species":"in_vitro","speciesRaw":"other animal (beagle dog); in vitro also","design":"randomized crossover (three-period crossover)","n":"6","status":"complete","statusNote":"","conclusion":"It was concluded that nanostructured lipid carriers were potential drug delivery systems to improve the bioavailability of silymarin. Other than improved dissolution, alternative mechanisms such as facilitated absorption as well as lymphatic transport may contribute to bioavailability enhancement.","limitations":"n = 6 dogs; washout not stated; variance type for PK table not stated; no individual-isomer data; dose given as silybin-equivalent only"},"24039417":{"pmid":"24039417","title":"Silymarin-loaded solid nanoparticles provide excellent hepatic protection: physicochemical characterization and in vivo evaluation.","authors":"Yang KY, Hwang du H, Yousaf AM, Kim DW, Shin YJ, Bae ON, Kim YI, Kim JO, Yong CS, Choi HG","journal":"International journal of nanomedicine","year":"2013","volume":"8","issue":"","pages":"3333-43","doi":"10.2147/IJN.S50683","url":"https://pubmed.ncbi.nlm.nih.gov/24039417/","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups)","n":"12 (PK)","status":"complete","statusNote":"Rat oral PK (n=6/group) of silymarin nanoparticles vs commercial product (Legalon); also dissolution and CCl4 hepatoprotection (not extracted).","conclusion":"Silymarin-loaded nanoparticles developed using SPG membrane emulsification and spray-drying techniques could be a useful system for delivery of poorly water-soluble silymarin while affording excellent hepatic protection.","limitations":"rat study, small n (6/group); no oral powder PK arm; specific sampling times not stated in text; analyte reported only as 'silymarin' (no individual flavonolignan quantification); no IV arm so absolute bioavailability not determined"},"24251357":{"pmid":"24251357","title":"Changes in pharmacokinetic profiles of acetaminophen and its glucuronide after pretreatment with combinations of N-acetylcysteine and either glycyrrhizin, silibinin or spironolactone in rat.","authors":"Xu R, Wang Q, Zhang J, Zang M, Liu X, Yang J","journal":"Xenobiotica; the fate of foreign compounds in biological systems","year":"2014","volume":"44","issue":"6","pages":"541-6","doi":"10.3109/00498254.2013.858849","url":"https://pubmed.ncbi.nlm.nih.gov/24251357/","species":"rodent","speciesRaw":"rodent","design":"parallel (5 groups)","n":"25","status":"off-target analyte","statusNote":"PK study of acetaminophen (APAP) and APAP glucuronide in rats; silibinin was given orally as a pretreatment (with NAC) but silibinin itself was not measured in any matrix.","conclusion":"SIB did not significantly change the PK profiles of these two substances.","limitations":"silibinin concentrations not measured; rat study n=5/group; APAP given i.p."},"24317417":{"pmid":"24317417","title":"Development and validation of two liquid chromatography-tandem mass spectrometry methods for the determination of silibinin and silibinin hemisuccinate in human plasma.","authors":"Sala F, Albares P, Colovic M, Persiani S, Rovati LC","journal":"Journal of chromatography. B, Analytical technologies in the biomedical and life sciences","year":"2014","volume":"945-946","issue":"","pages":"1-9","doi":"10.1016/j.jchromb.2013.11.028","url":"https://pubmed.ncbi.nlm.nih.gov/24317417/","species":"human","speciesRaw":"human","design":"randomized crossover (described as randomized, open-label, crossover study)","n":"6","status":"partial","statusNote":"Primary focus is LC-MS/MS method validation; PK data only as a brief application to IV Legalon SIL (silibinin hemisuccinate) in 6 healthy men; no oral absorption.","conclusion":"The methods were suitable for pharmacokinetic studies and were successfully applied to human plasma samples from subjects treated intravenously with Legalon SIL at the dose of 20 mg/kg, expressed as silibinin.","limitations":"method-validation paper; PK shown only briefly; IV only, no oral data; n=6; no t1/2 or other parameters reported in text; Fig. 4 shows one volunteer's profile (figure-only)"},"24495272":{"pmid":"24495272","title":"In vivo absorption comparison of nanotechnology-based silybin tablets with its water-soluble derivative.","authors":"Xu D, Ni R, Sun W, Li LC, Mao S","journal":"Drug development and industrial pharmacy","year":"2015","volume":"41","issue":"4","pages":"552-9","doi":"10.3109/03639045.2014.884123","url":"https://pubmed.ncbi.nlm.nih.gov/24495272/","species":"other_animal","speciesRaw":"other animal (rat; Beagle dog)","design":"rat: parallel (3 suspensions); dog: randomized crossover (stated as cross-over with 1 week washing period; randomization not stated)","n":"rats 18 (6 per suspension); dogs 6","status":"complete","statusNote":"","conclusion":"In vivo absorption study in Beagle dogs demonstrated that the bioavailability of silybin from the nanocrystal tablets was comparable with that of its water-soluble salt form in silybin meglumine tablets.","limitations":"no variance (SD) reported for PK parameters; small n; animal study (rat, dog); fed/fasted state NR; raw Cmax/AUC in dogs differ (Table 3: T 3600.95 vs R 2621.55 for AUC0-24) while text reports comparable after dose adjustment; oral industry funding (Abbott)"},"24766208":{"pmid":"24766208","title":"A novel solid dispersion system for natural product-loaded medicine: silymarin-loaded solid dispersion with enhanced oral bioavailability and hepatoprotective activity.","authors":"Hwang du H, Kim YI, Cho KH, Poudel BK, Choi JY, Kim DW, Shin YJ, Bae ON, Yousaf AM, Yong CS, Kim JO, Choi HG","journal":"Journal of microencapsulation","year":"2014","volume":"31","issue":"7","pages":"619-26","doi":"10.3109/02652048.2014.911375","url":"https://pubmed.ncbi.nlm.nih.gov/24766208/","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups)","n":"12","status":"complete","statusNote":"","conclusion":"The SD improved the bioavailability of drug by about 3-fold compared to commercial product in rats. Thus, the silymarin-loaded SD prepared with water, PVP and Tween 80 would be useful to deliver poorly water-soluble silymarin with improved bioavailability.","limitations":"rat study, n=6/group; no powder oral PK arm; sampling times not stated in text; fed/fasted state NR; analyte reported as silybin only"},"25149982":{"pmid":"25149982","title":"Silymarin liposomes improves oral bioavailability of silybin besides targeting hepatocytes, and immune cells.","authors":"Kumar N, Rai A, Reddy ND, Raj PV, Jain P, Deshpande P, Mathew G, Kutty NG, Udupa N, Rao CM","journal":"Pharmacological reports : PR","year":"2014","volume":"66","issue":"5","pages":"788-98","doi":"10.1016/j.pharep.2014.04.007","url":"https://pubmed.ncbi.nlm.nih.gov/25149982/","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups)","n":"12","status":"complete","statusNote":"","conclusion":"Incorporating phytosomal form of silymarin in liposomal carrier system showed better in vitro and in vivo hepatoprotection besides showing better anti-inflammatory effects and improvement in histopathological changes as compared to silymarin suspension. These effects were further supported by increase in AUC and Cmax of silybin by silymarin-liposomes compared to silymarin suspension.","limitations":"rat study, n=6/group; no statistical test reported for PK parameters; sampling window only up to 2 h per text (AUC0-2); AUC0-inf extrapolated; clearance and Vd not scaled to dose/bioavailability; only silybin quantified (A and B averaged)"},"25375210":{"pmid":"25375210","title":"Silymarin in liposomes and ethosomes: pharmacokinetics and tissue distribution in free-moving rats by high-performance liquid chromatography-tandem mass spectrometry.","authors":"Chang LW, Hou ML, Tsai TH","journal":"Journal of agricultural and food chemistry","year":"2014","volume":"62","issue":"48","pages":"11657-65","doi":"10.1021/jf504139g","url":"https://pubmed.ncbi.nlm.nih.gov/25375210/","species":"rodent","speciesRaw":"rodent","design":"parallel (3 formulations x IV and oral groups)","n":"NR","status":"complete","statusNote":"","conclusion":"These results showed that the LSM and ESM encapsulated formulations of silymarin may provide more efficient tissue distribution and increased oral bioavailability, thus improving its therapeutic bioactive properties in the body.","limitations":"rat study, n=5; dose basis (silymarin vs silibinin content) not stated; oral bioavailability computed against IV of free silymarin only; oral CL printed in same units as IV CL; PK sampling times not stated in text; Cmax of free silymarin PO very low (0.02 µg/mL)"},"25544390":{"pmid":"25544390","title":"A comparative study on the therapeutic effects of silymarin and silymarin-loaded solid lipid nanoparticles on D-GaIN/TNF-α-induced liver damage in Balb/c mice.","authors":"Cengiz M, Kutlu HM, Burukoglu DD, Ayhancı A","journal":"Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association","year":"2015","volume":"77","issue":"","pages":"93-100","doi":"10.1016/j.fct.2014.12.011","url":"https://pubmed.ncbi.nlm.nih.gov/25544390/","species":"rodent","speciesRaw":"rodent","design":"parallel (5 groups of 7)","n":"35","status":"not absorption-related","statusNote":"Hepatoprotection study (D-GalN/TNF-alpha liver injury in mice; histology and Bcl-2/Bax/PCNA immunohistochemistry) of silymarin vs silymarin-loaded solid lipid nanoparticles. No plasma/tissue concentrations, PK parameters or absorption measurements. Only formulation particle size and zeta potential reported; bioavailability is mentioned only as a hypothesis.","conclusion":"Sm-loaded SLN could be a useful system for the delivery of poorly water-soluble Sm, apart from providing favourable hepatic protection.","limitations":"no absorption or PK data; bioavailability enhancement claimed but not measured"},"25735668":{"pmid":"25735668","title":"Development, optimization and evaluation of long chain nanolipid carrier for hepatic delivery of silymarin through lymphatic transport pathway.","authors":"Chaudhary S, Garg T, Murthy RS, Rath G, Goyal AK","journal":"International journal of pharmaceutics","year":"2015","volume":"485","issue":"1-2","pages":"108-21","doi":"10.1016/j.ijpharm.2015.02.070","url":"https://pubmed.ncbi.nlm.nih.gov/25735668/","species":"rodent","speciesRaw":"rodent","design":"parallel (3 groups)","n":"18 (PK)","status":"complete","statusNote":"","conclusion":"It was evident from the findings that the silymarin loaded NLCs exhibited selective liver uptake through the chylomicron pathway. Therefore, it was concluded that lipid carrier systems utilize the chylomicron pathway for the selective transport of drug entrapped in them to the liver cells.","limitations":"rat study; no statistical tests reported for PK parameters; variance only printed for Cmax; internal inconsistencies (Cmax 25.565 vs 25.525; suspension Tmax 4 vs 5 h; sex of rats); dose basis (silymarin vs silybin content) not stated; tissue concentrations lack n"},"25848259":{"pmid":"25848259","title":"Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery.","authors":"Chen CH, Chang CC, Shih TH, Aljuffali IA, Yeh TS, Fang JY","journal":"International journal of nanomedicine","year":"2015","volume":"10","issue":"","pages":"2403-16","doi":"10.2147/IJN.S79522","url":"https://pubmed.ncbi.nlm.nih.gov/25848259/","species":"rodent","speciesRaw":"rodent","design":"parallel (formulation x surgery groups)","n":"NR","status":"complete","statusNote":"","conclusion":"Our pharmacokinetic results indicate that SNEDDS increase the bioavailability of silibinin above that achieved by suspension and solution formulations of silymarin.","limitations":"rat model (RYGB) with n=5-10 per group stated as a range; dose basis ambiguous (24% vs 45% silibinin content); sham group not used for PK comparison (normal rats used); table units/significance details partly in figures"},"25956049":{"pmid":"25956049","title":"Comparison of the oral bioavailability of silymarin-loaded lipid nanoparticles with their artificial lipolysate counterparts: implications on the contribution of integral structure.","authors":"Shangguan M, Qi J, Lu Y, Wu W","journal":"International journal of pharmaceutics","year":"2015","volume":"489","issue":"1-2","pages":"195-202","doi":"10.1016/j.ijpharm.2015.05.005","url":"https://pubmed.ncbi.nlm.nih.gov/25956049/","species":"other_animal","speciesRaw":"other animal (beagle dog)","design":"randomized crossover (six-period crossover; randomization not stated)","n":"6","status":"complete","statusNote":"Beagle dog (animal) crossover PK of silymarin (silybin measured) as lipid nanoparticles vs lipolysates vs solid dispersion mixtures; supplement is milk thistle/silymarin (on-target, animal study, oral gavage)","conclusion":"The lipid nanoparticles could be transformed into lipolysates by conventional lipolysis procedures. Approximately 80% of the drug could be transferred into the hydrotropic phase. The lipid nanoparticles showed higher oral bioavailability than their lipolysate counterparts, with the bioavailability of lipolysates of NLCs and SLNs being approximately 75% and 60%, respectively. Therefore, we propose that lipolysis is the predominating mechanism governing oral absorption for lipid nanoparticles. The integral structure of the vehicles contributed only trivially to the overall bioavailability.","limitations":"animal study (six beagle dogs); small n; tables do not state variance type or statistic type; no washout or randomization details reported; sampling times not stated in text; Cmax/AUC reported for silybin only (as marker of silymarin); drug precipitation in in vitro lipolysates (~20%) may affect interpretation"},"26068528":{"pmid":"26068528","title":"Improvement bioavailability of silymarin ameliorates severe dyslipidemia associated with metabolic syndrome.","authors":"Poruba M, Kazdová L, Oliyarnyk O, Malinská H, Matusková Z, Tozzi di Angelo I, Skop V, Vecera R","journal":"Xenobiotica; the fate of foreign compounds in biological systems","year":"2015","volume":"45","issue":"9","pages":"751-6","doi":"10.3109/00498254.2015.1010633","url":"https://pubmed.ncbi.nlm.nih.gov/26068528/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"not absorption-related","statusNote":"Rat pharmacodynamic study (plasma/liver lipids, hepatic CYP7A1, CYP4A, ABCG5/8 protein expression) of dietary 1% standardized, micronized and phytosome silymarin; no silymarin/silybin concentration, PK or absorption measurement. Bioavailability differences are only cited from other work.","conclusion":"Silymarin in the form of phytosome and micronized silymarin are more effective forms of silymarin than standardized silymarin extract, probably due to their better bioavailability.","limitations":"no PK or absorption data measured; bioavailability claim is inferred from other studies, not measured"},"26152876":{"pmid":"26152876","title":"Preparation and performance evaluation of emulsomes as a drug delivery system for silybin.","authors":"Zhou X, Chen Z","journal":"Archives of pharmacal research","year":"2015","volume":"38","issue":"12","pages":"2193-200","doi":"10.1007/s12272-015-0630-7","url":"https://pubmed.ncbi.nlm.nih.gov/26152876/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"12","status":"complete","statusNote":"Silybin given intravenously to rats (emulsomes vs solution); on-target, IV route (no oral absorption); in vitro release also reported","conclusion":"Compared to an SIL solution, emulsomes produced sustained release of SIL for up to 48 h after an initial burst release in vitro. ... Following SIL delivery by emulsomes, the area under the curve was 2.2-fold higher and the mean residence time was 2.5-fold higher than the corresponding values recorded using SIL solution. Hence, emulsomes might represent a promising system for improving the bioavailability of lipophilic drugs.","limitations":"intravenous only, no oral absorption data; small n (6 per group); AUC interval not stated; in vitro release values approximate; plasma profile figure-only"},"26222744":{"pmid":"26222744","title":"Serum and tissue pharmacokinetics of silibinin after per os and i.v. administration to mice as a HP-β-CD lyophilized product.","authors":"Christodoulou E, Kechagia IA, Tzimas S, Balafas E, Kostomitsopoulos N, Archontaki H, Dokoumetzidis A, Valsami G","journal":"International journal of pharmaceutics","year":"2015","volume":"493","issue":"1-2","pages":"366-73","doi":"10.1016/j.ijpharm.2015.07.060","url":"https://pubmed.ncbi.nlm.nih.gov/26222744/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"60","status":"complete","statusNote":"Silibinin (SLB) as HP-β-CD lyophilized product, oral and IV, mice; on-target; brain/spleen tissue samples collected but no values reported","conclusion":"Absolute oral bioavailability of SLB from the lyophilized HP-β-CD-SLB product was found about 50% for total (metabolized and non-metabolized) and 10% for parent (non-metabolized) SLB i.e. 10 times higher that after administration of pure SLB.","limitations":"sparse sampling, one time point per group of 5 mice (naïve pooled analysis); comparator pure-silibinin data are from a different study in rats; metabolite values calculated by subtraction; dose stated differently in abstract and methods; no fed/fasted status stated; PK variance expressed as %RSE only"},"26433256":{"pmid":"26433256","title":"Nano-silymarin provides protection against γ-radiation-induced oxidative stress in cultured human embryonic kidney cells.","authors":"Adhikari M, Arora R","journal":"Mutation research. Genetic toxicology and environmental mutagenesis","year":"2015","volume":"792","issue":"","pages":"1-11","doi":"10.1016/j.mrgentox.2015.08.006","url":"https://pubmed.ncbi.nlm.nih.gov/26433256/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro)","n":"NR","status":"not absorption-related","statusNote":"In vitro radioprotection study of nano-silymarin (SNEDDS) in HEK cells (plasmid relaxation, MTT, micronucleus, ROS, cell cycle) and formulation characterization; no absorption/PK measurement. Bioavailability is mentioned only as rationale.","conclusion":"Nano-silymarin was radioprotective, supporting the possibility of developing new approaches to radiation protection via nanotechnology.","limitations":"no PK or absorption data measured"},"26543366":{"pmid":"26543366","title":"Enhanced oral bioavailability of silymarin using liposomes containing a bile salt: preparation by supercritical fluid technology and evaluation in vitro and in vivo.","authors":"Yang G, Zhao Y, Zhang Y, Dang B, Liu Y, Feng N","journal":"International journal of nanomedicine","year":"2015","volume":"10","issue":"","pages":"6633-44","doi":"10.2147/IJN.S92665","url":"https://pubmed.ncbi.nlm.nih.gov/26543366/","species":"rodent","speciesRaw":"rodent","design":"parallel (randomly assigned to five groups)","n":"NR","status":"complete","statusNote":"Rat oral PK of silymarin as bile-salt liposomes (three preparation methods) vs powder and commercial tablet; plus in vitro characterization","conclusion":"In vivo assays showed enhanced oral bioavailability of SM administered in liposomes containing a bile salt when compared with an aqueous SM suspension or commercial SM product. This indicates that SEDS exhibit great potential for the preparation of liposomes with improved solubility and oral bioavailability of SM.","limitations":"rat study, n=6 per group; sampling times not listed in text; AUC0-t last time point not stated; plasma concentration profile figure-only; no direct statistical comparison between liposome methods"},"26556526":{"pmid":"26556526","title":"Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration.","authors":"Han X, Wang Z, Wang M, Li J, Xu Y, He R, Guan H, Yue Z, Gong M","journal":"Drug delivery","year":"2016","volume":"23","issue":"5","pages":"1818-29","doi":"10.3109/10717544.2015.1108374","url":"https://pubmed.ncbi.nlm.nih.gov/26556526/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"18 (PK rats)","status":"complete","statusNote":"Rat oral PK of silybin as HA-DOCA / HA-GA micelles vs suspension, plus in situ intestinal perfusion (Peff) and in vitro release. Mouse DiR imaging and CCl4 efficacy are not absorption values (liver targeting qualitative only).","conclusion":"The silybin-loaded micelles could be absorbed in the whole intestine through a passive diffusion mechanism and achieved significantly higher oral bioavailability compared with suspension formulation. ... Therefore, HA-adh-GA20 conjugates show great potential for improving the bioavailability and liver targetability of silybin after oral administration.","limitations":"rat study, n=6 per group; feeding status of PK rats not stated; AUC0-t end time not stated; Peff numbers given in text only for DOCA10 ileum; others figure-only; tmax printed without variance"},"26595166":{"pmid":"26595166","title":"The influence of ABCB1 polymorphism C3435T on the pharmacokinetics of silibinin.","authors":"Tan ZR, Zhou YX, Liu J, Huang WH, Chen Y, Wang YC, Wang LS","journal":"Journal of clinical pharmacy and therapeutics","year":"2015","volume":"40","issue":"6","pages":"685-8","doi":"10.1111/jcpt.12336","url":"https://pubmed.ncbi.nlm.nih.gov/26595166/","species":"human","speciesRaw":"human","design":"single-arm","n":"23","status":"complete","statusNote":"Healthy Chinese men, single 140 mg silymarin capsule (Legalon), silibinin PK stratified by ABCB1 C3435T genotype","conclusion":"This study shows that the pharmacokinetics of silibinin is significantly influenced by ABCB1 C3435T polymorphism, Dosage adjustment may be necessary for subjects of different genotypes to ensure comparative exposures. A dose-ranging clinical trial should be undertaken to determine whether the observed differences are clinically significant.","limitations":"small genotype groups (n=5 to 10); men only; single dose, no comparator formulation; silibinin glucuronide not measured; dose basis (silibinin content) NR"},"26642669":{"pmid":"26642669","title":"RATIONALIZED AND COMPLEMENTARY FINDINGS OF SILYMARIN (MILK THISTLE) IN PAKISTANI HEALTHY VOLUNTEERS.","authors":"Ashraf M, Abid F, Riffat S, Bashir S, Iqbal J, Sarfraz M, Afzal A, Zaheer M","journal":"Acta poloniae pharmaceutica","year":"2015","volume":"72","issue":"3","pages":"607-14","doi":"NR","url":"https://pubmed.ncbi.nlm.nih.gov/26642669/","species":"human","speciesRaw":"human","design":"parallel (comparative parallel design by gender)","n":"16","status":"complete","statusNote":"Gender comparison of oral silymarin PK (200 mg tablet) in 8 male and 8 female Pakistani volunteers","conclusion":"On the bases of observed variations in pharmacokinetics of silymarin in male and female it will be right to say that gender based evidence should be provided if clinical study is reported especially on human being. It is evident that the dose of silymarin must be adjusted prior to administration according to demographic parameters of the patient.","limitations":"n=8 per sex; units missing in Table 3 for several parameters; dose basis NR; very small SDs raise concern; blank plasma from a blood bank used for validation; parallel design: sex confounded with body size; unpaired t-test only"},"26669888":{"pmid":"26669888","title":"In Vitro Release and Bioavailability of Silybin from Micelle-Templated Porous Calcium Phosphate Microparticles.","authors":"Zhu Y, Wang M, Zhang Y, Zeng J, Omari-Siaw E, Yu J, Xu X","journal":"AAPS PharmSciTech","year":"2016","volume":"17","issue":"5","pages":"1232-9","doi":"10.1208/s12249-015-0460-4","url":"https://pubmed.ncbi.nlm.nih.gov/26669888/","species":"other_animal","speciesRaw":"other animal (beagle dog)","design":"randomized crossover (4 dogs randomly and equally divided into two groups)","n":"4","status":"complete","statusNote":"Beagle dog crossover oral PK of silybin as porous calcium phosphate microparticles vs free silybin; plus in vitro release and IVIVC","conclusion":"In summary, a novel porous calcium phosphate microparticle based on povidone/sodium cholate/phospholipid mixed micelles was prepared successfully for the first time. The pharmacokinetic study in beagle dogs showed the enhanced oral bioavailability facilitated by the prepared microparticle.","limitations":"n=4 dogs; no p-values given for Cmax/AUC; t1/2 and MRT (>34 h) exceed 24 h sampling window; Tmax printed without variance; relative bioavailability calculation basis not stated"},"26674103":{"pmid":"26674103","title":"A New Type of Liquid Silymarin Proliposome Containing Bile Salts: Its Preparation and Improved Hepatoprotective Effects.","authors":"Wang M, Xie T, Chang Z, Wang L, Xie X, Kou Y, Xu H, Gao X","journal":"PloS one","year":"2015","volume":"10","issue":"12","pages":"e0143625","doi":"10.1371/journal.pone.0143625","url":"https://pubmed.ncbi.nlm.nih.gov/26674103/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro everted gut sac, liposome vs solution)","n":"NR","status":"partial","statusNote":"Primary report is formulation development plus hepatoprotection in mice; the only absorption data are in vitro everted rat gut sac transport (Tables 4-5). No in vivo PK.","conclusion":"According to the simple everted rat sac transport experiments, silymarin liposome transport across the intestinal barrier is better than for a silymarin solution, which shows that silymarin liposomes are a potential delivery system for silymarin to improve its bioavailability in vivo.","limitations":"in vitro everted sac only; no in vivo PK; n inconsistent (5 in tables vs triplicate/six sacs in Methods); variance type of tables not labelled; AUC interval and dose not stated; silymarin quantified by UV, not specific flavonolignans"},"26681893":{"pmid":"26681893","title":"Stability studies of silymarin nanoemulsion containing Tween 80 as a surfactant.","authors":"Parveen R, Baboota S, Ali J, Ahuja A, Ahmad S","journal":"Journal of pharmacy & bioallied sciences","year":"2015","volume":"7","issue":"4","pages":"321-4","doi":"10.4103/0975-7406.168037","url":"https://pubmed.ncbi.nlm.nih.gov/26681893/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation stability)","n":"NR","status":"not absorption-related","statusNote":"Physicochemical shelf-life/stability study of a silymarin nanoemulsion at 5, 25 and 40 C over 90 days (HPTLC silybin content, droplet size, viscosity). No absorption or pharmacokinetic data reported.","conclusion":"These results indicated that stability of silymarin can be enhanced in nanoemulsion formulation using Tween 80 as a surfactant.","limitations":"no absorption/PK data"},"26770331":{"pmid":"26770331","title":"Pharmacokinetics of silybin nanoparticles in mice bearing SKOV-3 human ovarian carcinoma xenocraft.","authors":"Guan XL, Zhao SZ, Hou RJ, Yang SH, Zhang QL, Yin SL, Wang SJ","journal":"International journal of clinical and experimental medicine","year":"2015","volume":"8","issue":"10","pages":"17406-17","doi":"NR","url":"https://pubmed.ncbi.nlm.nih.gov/26770331/","species":"rodent","speciesRaw":"rodent","design":"randomized crossover","n":"12","status":"complete","statusNote":"","conclusion":"Complex of silybin with nanoparticle prompted sustained release of the drug in vitro and enhanced bioavailability in vivo.","limitations":"small n (12 rats); tumor-bearing animal model; internal inconsistencies (species, Cmax text vs table, fold-changes); variance type not stated; sampling times not stated; CL and Vd printed with unit mg/ml; funding not reported"},"26875177":{"pmid":"26875177","title":"Effects of Aqueous Extracts of Chicory and Milk Thistle on Serum Concentrations of Copper, Zinc, and Manganese in Tamoxifen-Treated Rats.","authors":"Abbasalipourkabir R, Ziamajidi N, Nasiri A, Behrouj H","journal":"Biological trace element research","year":"2016","volume":"173","issue":"1","pages":"140-3","doi":"10.1007/s12011-016-0629-z","url":"https://pubmed.ncbi.nlm.nih.gov/26875177/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"36","status":"off-target analyte","statusNote":"Measures serum Cu, Zn and Mn in tamoxifen-treated rats given aqueous milk thistle seed extract (1.6 g/kg/day gavage, 14 days); no silymarin/silybin or milk-thistle compound was measured, so no absorption/PK of the supplement.","conclusion":"it is suggested that chicory and milk thistle extracts may ameliorate the effects of tamoxifen on the trace element levels in the body, although further investigations are needed to determine the effects of these components on other trace elements and antioxidant status.","limitations":"analytes are minerals, not the supplement; small n; extract composition not characterised"},"27436270":{"pmid":"27436270","title":"Highly bioavailable silibinin nanoparticles inhibit HCV infection.","authors":"Liu CH, Lin CC, Hsu WC, Chung CY, Lin CC, Jassey A, Chang SP, Tai CJ, Tai CJ, Shields J, Richardson CD, Yen MH, Tyrrell DLJ, Lin LT","journal":"Gut","year":"2017","volume":"66","issue":"10","pages":"1853-1861","doi":"10.1136/gutjnl-2016-312019","url":"https://pubmed.ncbi.nlm.nih.gov/27436270/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"partial","statusNote":"Rat PK and biodistribution results (Fig 6) are shown only as figures; text gives only qualitative statements and a 2 h peak time for SB-NP. Most of the paper is anti-HCV in vitro work.","conclusion":"we have successfully developed SB-NPs exhibiting potent anti-HCV and antioxidant efficacy, with improved solubility and bioavailability.","limitations":"PK values figure-only; no PK parameters (Cmax, AUC) reported; single dose 100 mg/kg in rats; vehicle and fasting not stated; statistical comparison for PK not stated"},"27517806":{"pmid":"27517806","title":"Modulatory effects of silibinin in various cell signaling pathways against liver disorders and cancer - A comprehensive review.","authors":"Polachi N, Bai G, Li T, Chu Y, Wang X, Li S, Gu N, Wu J, Li W, Zhang Y, Zhou S, Sun H, Liu C","journal":"European journal of medicinal chemistry","year":"2016","volume":"123","issue":"","pages":"577-595","doi":"10.1016/j.ejmech.2016.07.070","url":"https://pubmed.ncbi.nlm.nih.gov/27517806/","species":"other_animal","speciesRaw":"other animal (specify)","design":"other (review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review (Eur J Med Chem) of silibinin pharmacokinetics, bioavailability, clinical effects and signalling pathways; not a primary study.","conclusion":"()","limitations":"review article, no primary data extracted"},"27575878":{"pmid":"27575878","title":"A new drug nanocrystal self-stabilized Pickering emulsion for oral delivery of silybin.","authors":"Yi T, Liu C, Zhang J, Wang F, Wang J, Zhang J","journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences","year":"2017","volume":"96","issue":"","pages":"420-427","doi":"10.1016/j.ejps.2016.08.047","url":"https://pubmed.ncbi.nlm.nih.gov/27575878/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"complete","statusNote":"","conclusion":"With a core–shell structure and good physical stability, SN-SSPE could increase the dissolution rate and oral bioavailability of silybin.","limitations":"rat study only; single dose; n=6; no IV reference so no absolute bioavailability; double-peak profile; text-table inconsistency on early plasma concentration"},"28098838":{"pmid":"28098838","title":"Role of UDP-Glucuronosyltransferase 1A1 in the Metabolism and Pharmacokinetics of Silymarin Flavonolignans in Patients with HCV and NAFLD.","authors":"Xie Y, Miranda SR, Hoskins JM, Hawke RL","journal":"Molecules (Basel, Switzerland)","year":"2017","volume":"22","issue":"1","pages":"","doi":"10.3390/molecules22010142","url":"https://pubmed.ncbi.nlm.nih.gov/28098838/","species":"human","speciesRaw":"human","design":"other (secondary analysis of Phase 1 randomized dose-escalation trial, SyNCH, NCT00389376, plus in vitro enzyme kinetics)","n":"29 analysed for genotype-PK (56 enrolled; 33 genotyped)","status":"complete","statusNote":"","conclusion":"our results indicate the UGT1A1*28 allele has no significant effect on the pharmacokinetics of silybin A and silybin B in patients with NAFLD or chronic HCV infection.","limitations":"small n per genotype (5 for *28/*28); doses pooled across 140-700 mg cohorts (dose-normalized); mixed HCV and NAFLD patients; dosing schedule and fed/fasted state not stated in this paper; conjugate profile from pooled plasma; secondary analysis"},"28503949":{"pmid":"28503949","title":"Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization.","authors":"Ahmad U, Akhtar J, Singh SP, Ahmad FJ, Siddiqui S","journal":"Artificial cells, nanomedicine, and biotechnology","year":"2018","volume":"46","issue":"2","pages":"231-241","doi":"10.1080/21691401.2017.1324465","url":"https://pubmed.ncbi.nlm.nih.gov/28503949/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"complete","statusNote":"","conclusion":"Our results concluded that nanoemulsion may be an efficient carrier for oral delivery of silymarin against human hepatocellular carcinoma without damaging normal cells.","limitations":"rat study only; doses differ between arms (42, 35, 20 mg/kg); n inconsistent (6 vs 3); fasting state not stated; silymarin measured by HPTLC (not individual flavonolignans); single dose"},"28553075":{"pmid":"28553075","title":"Fabrication, characterization and in vitro evaluation of silibinin nanoparticles: an attempt to enhance its oral bioavailability.","authors":"Sahibzada MUK, Sadiq A, Khan S, Faidah HS, Naseemullah, Khurram M, Amin MU, Haseeb A","journal":"Drug design, development and therapy","year":"2017","volume":"11","issue":"","pages":"1453-1464","doi":"10.2147/DDDT.S133806","url":"https://pubmed.ncbi.nlm.nih.gov/28553075/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation characterization)","n":"NR","status":"partial","statusNote":"In vitro solubility and dissolution of silibinin nanoparticles only; no absorption or PK in animals or humans. Paper also reports antimicrobial MICs (not extracted).","conclusion":"the NPs of silibinin prepared by the APSP and EPN methods are highly soluble, with a higher dissolution rate compared to that of unprocessed silibinin.","limitations":"in vitro only; no in vivo absorption data; no statistical tests for solubility/dissolution reported; dissolution time-course values only in figure"},"28602600":{"pmid":"28602600","title":"Influence of the dual combination of silymarin and (-)-epigallocatechin gallate, natural dietary flavonoids, on the pharmacokinetics of oxcarbazepine in rats.","authors":"Ferreira A, Rodrigues M, Marques A, Falcão A, Alves G","journal":"Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association","year":"2017","volume":"106","issue":"Pt A","pages":"446-454","doi":"10.1016/j.fct.2017.06.015","url":"https://pubmed.ncbi.nlm.nih.gov/28602600/","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, rat PK drug-interaction study; verapamil positive control; no vehicle control group in this study)","n":"36 (PK study); 12 (plasma-to-brain study)","status":"off-target analyte","statusNote":"PK study of oxcarbazepine (OXC) and its metabolite licarbazepine (LIC) in rats after i.p. pre-treatment with silymarin, EPG or silymarin/EPG as P-gp inhibitors. Silymarin/silybinin was not measured in plasma or brain; only OXC and LIC were assayed. No silymarin absorption data to extract.","conclusion":"These findings evidence the synergistic effect of silymarin and EPG in enhancing the degree of systemic exposure to OXC and LIC in rats, which occurred in a comparable extent to that observed with verapamil.","limitations":"silymarin itself not measured; no vehicle control group in this experiment; i.p. route"},"28643437":{"pmid":"28643437","title":"Silibinin affects the pharmacokinetics of methadone in rats.","authors":"Pan PP, Wang J, Luo J, Wang SH, Zhou YF, Chen SZ, Du Z","journal":"Drug testing and analysis","year":"2018","volume":"10","issue":"3","pages":"557-561","doi":"10.1002/dta.2235","url":"https://pubmed.ncbi.nlm.nih.gov/28643437/","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, rat PK drug-interaction study)","n":"24","status":"off-target analyte","statusNote":"PK drug-interaction study in rats: silibinin (oral, single or 14-day multiple dose) given before oral methadone; only methadone and its metabolite EDDP were measured in plasma. Silibinin concentrations were not measured, so no silibinin absorption data to extract.","conclusion":"It is concluded that silibinin significantly altered the pharmacokinetics of methadone in rats by increasing the exposure of methadone.","limitations":"silibinin itself not measured"},"28778838":{"pmid":"28778838","title":"In vivo fate of lipid-silybin conjugate nanoparticles: Implications on enhanced oral bioavailability.","authors":"Ma Y, He H, Xia F, Li Y, Lu Y, Chen D, Qi J, Lu Y, Zhang W, Wu W","journal":"Nanomedicine : nanotechnology, biology, and medicine","year":"2017","volume":"13","issue":"8","pages":"2643-2654","doi":"10.1016/j.nano.2017.07.014","url":"https://pubmed.ncbi.nlm.nih.gov/28778838/","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, rat oral PK vs reference formulation; plus in vitro Caco-2 models, lymph cannulation, imaging)","n":"NR","status":"complete","statusNote":"Oral PK of silybin in rats from lipid-silybin conjugate SLNs vs fast-release SB pellets; plus in vitro Caco-2 and lymph transport. Variance (±) type not defined in main text (supplement not seen).","conclusion":"The oral bioavailability of SB is enhanced by 5-7-fold in comparison with a fast-release formulation. No integral LDCs are detected in plasma confirms the readily degradable nature of LDCs.","limitations":"Variance type for ± values not stated in main text; Rat strain/sex/dose volume and plasma sampling times only in supporting information or figure; n_total NR; Some values figure-only (Fig. 4, 5, 6); 18C-SB purity 85.0%"},"28952834":{"pmid":"28952834","title":"Silibinin Effect on Fas/FasL, HMGB1, and CD45 Expressions in a Rat Model Subjected to Liver Ischemia-Reperfusion Injury.","authors":"Tsaroucha AK, Valsami G, Kostomitsopoulos N, Lambropoulou M, Anagnostopoulos C, Christodoulou E, Falidas E, Betsou A, Pitiakoudis M, Simopoulos CE","journal":"Journal of investigative surgery : the official journal of the Academy of Surgical Research","year":"2018","volume":"31","issue":"6","pages":"491-502","doi":"10.1080/08941939.2017.1360416","url":"https://pubmed.ncbi.nlm.nih.gov/28952834/","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, rat I/R model with IV silibinin; sparse-sampling PK)","n":"73","status":"complete","statusNote":"Primary aim is hepatoprotection (immunohistochemistry); silibinin PK after IV SLB-HP-β-CD in healthy (PK group) and ischemia-reperfusion (Si group) rats is also reported. IV route, so absorption not assessed; PK extracted as on-target (IV).","conclusion":"In conclusion, in the present study, the hepatoprotective and anti-inflammatory effect of the antioxidant agent silibinin was demonstrated through the reduction of the expression of specific biomarkers, Fas/FasL, HMGB-1, CD45, in liver tissue under I/R conditions.","limitations":"IV administration only; n per PK time point NR; sparse sampling NCA of mean curves; variance given only as % relative standard error; statistic type for PK parameters NR; values for several parameters figure-only (Figs 5, 6)"},"28958806":{"pmid":"28958806","title":"Role of tangeretin as a potential bioavailability enhancer for silybin: Pharmacokinetic and pharmacological studies.","authors":"Yuan ZW, Li YZ, Liu ZQ, Feng SL, Zhou H, Liu CX, Liu L, Xie Y","journal":"Pharmacological research","year":"2018","volume":"128","issue":"","pages":"153-166","doi":"10.1016/j.phrs.2017.09.019","url":"https://pubmed.ncbi.nlm.nih.gov/28958806/","species":"rodent","speciesRaw":"rodent","design":"other (parallel groups, rat PK with bioenhancer; in vitro transporter studies)","n":"18 (PK study, 3 groups of 6)","status":"complete","statusNote":"Mainly rat oral PK of silybin with/without tangeretin plus in vitro Caco-2/MDCKII/hepatocyte transport; CCl4 liver-injury pharmacology not extracted (not absorption). Some in vitro results are figure-only; supplementary data not in PDF.","conclusion":"pharmacokinetic and pharmacological studies demonstrated that tangeretin is a promising agent as bioenhancer for silybin by modulating the transporter of Mrp2 and Bcrp. The combination of tangeretin and silybin is certainly beneficial to improve bioavailability and therapeutic potential.","limitations":"variance type for in vitro values not defined; n for several in vitro rows not stated in text (figure captions n=3); Methods say geometric mean ± SD, Table 1 says mean ± SD; many in vitro values figure-only or in supplement; tangeretin PK not reported"},"29026299":{"pmid":"29026299","title":"Glycogen-gold nanohybrid escalates the potency of silymarin.","authors":"Kandimalla R, Dash S, Bhowal AC, Kalita S, Talukdar NC, Kundu S, Kotoky J","journal":"International journal of nanomedicine","year":"2017","volume":"12","issue":"","pages":"7025-7038","doi":"10.2147/IJN.S142497","url":"https://pubmed.ncbi.nlm.nih.gov/29026299/","species":"rodent","speciesRaw":"rodent","design":"parallel (4 groups), formulation comparison","n":"24","status":"complete","statusNote":"Rat oral PK of silymarin formulations (Cmax, Tmax only, Table S1 printed at end of PDF; full curves figure-only) plus CCl4 hepatoprotection (not extracted). List says species human but study is in rats.","conclusion":"Compared to free Sly, GSGNPs exhibited significant hepatoprotection with tenfold increase in the potency due to increased solubility, bioavailability, and profuse gut absorption.","limitations":"Only Cmax and Tmax reported; no AUC; Cmax/Tmax in supplementary table; full profile figure-only (Fig. 7); n per group stated in Methods only; commercial product dose basis NR; no conflict-of-interest/funding detail"},"29125572":{"pmid":"29125572","title":"Silybin, a Major Bioactive Component of Milk Thistle (Silybum marianum L. Gaernt.)-Chemistry, Bioavailability, and Metabolism.","authors":"Bijak M","journal":"Molecules (Basel, Switzerland)","year":"2017","volume":"22","issue":"11","pages":"","doi":"10.3390/molecules22111942","url":"https://pubmed.ncbi.nlm.nih.gov/29125572/","species":"other_animal","speciesRaw":"other animal (specify)","design":"other (narrative review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review of silybin chemistry, metabolism and bioavailability (Bijak, Molecules 2017); no original pharmacokinetic data. Pages 1-4 read; publication type listed as Review.","conclusion":"NR","limitations":"review article, no primary data"},"29162374":{"pmid":"29162374","title":"The efficiency and mechanism of N-octyl-O, N-carboxymethyl chitosan-based micelles to enhance the oral absorption of silybin.","authors":"Yin T, Zhang Y, Liu Y, Chen Q, Fu Y, Liang J, Zhou J, Tang X, Liu J, Huo M","journal":"International journal of pharmaceutics","year":"2018","volume":"536","issue":"1","pages":"231-240","doi":"10.1016/j.ijpharm.2017.11.034","url":"https://pubmed.ncbi.nlm.nih.gov/29162374/","species":"rodent","speciesRaw":"rodent","design":"parallel groups (5 groups), formulation comparison with i.v. reference","n":"25","status":"complete","statusNote":"Rat oral/i.v. PK of silybin formulations plus Caco-2 uptake and transport mechanism studies. Plasma samples were treated with beta-glucuronidase before HPLC, so reported plasma silybin is deconjugated (total) silybin.","conclusion":"OCC micelles were demonstrated to efficiently solubilize SLB into the inner cores. Moreover, OCC-SLB micelles allowed for significant increases in SLB oral bioavailability compared with the SLB suspension","limitations":"small n (5 per group); sex of rats NR; plasma values are after beta-glucuronidase treatment (total silybin); some in vitro data figure-only"},"29273470":{"pmid":"29273470","title":"Relative Bioavailability of Silybin A and Silybin B From 2 Multiconstituent Dietary Supplement Formulations Containing Milk Thistle Extract: A Single-dose Study.","authors":"Li WY, Yu G, Hogan RM, Mohandas R, Frye RF, Gumpricht E, Markowitz JS","journal":"Clinical therapeutics","year":"2018","volume":"40","issue":"1","pages":"103-113.e1","doi":"10.1016/j.clinthera.2017.11.013","url":"https://pubmed.ncbi.nlm.nih.gov/29273470/","species":"human","speciesRaw":"human","design":"randomized crossover (open-label)","n":"12","status":"complete","statusNote":"Randomized crossover relative bioavailability of silybin A and B (non-conjugated) from two multi-ingredient milk thistle supplements.","conclusion":"The IsaGenesis soft gel formulation provided substantially greater absorption and bioavailability of silybin A and silybin B relative to the powdered Product B supplement.","limitations":"sponsor funded by product manufacturer; multi-ingredient formulations; unequal silymarin content between products (dose corrected); only non-conjugated silybins measured; no p-values reported for main comparisons; single dose, small n"},"29710546":{"pmid":"29710546","title":"Pharmacokinetic interaction of diosmetin and silibinin with other drugs: Inhibition of CYP2C9-mediated biotransformation and displacement from serum albumin.","authors":"Poór M, Boda G, Mohos V, Kuzma M, Bálint M, Hetényi C, Bencsik T","journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","year":"2018","volume":"102","issue":"","pages":"912-921","doi":"10.1016/j.biopha.2018.03.146","url":"https://pubmed.ncbi.nlm.nih.gov/29710546/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro enzyme inhibition and protein binding)","n":"NR","status":"not absorption-related","statusNote":"In vitro drug-interaction study: inhibition of CYP2C9-mediated diclofenac 4'-hydroxylation (IC50 approx. 13 uM diosmetin, 33 uM warfarin, 45 uM silibinin) and albumin binding/warfarin displacement by diosmetin and silibinin (fluorescence, ultrafiltration, docking). No absorption, bioavailability or in vivo PK of silibinin is measured; pages 1-4 read.","conclusion":"It is demonstrated that DIO and SIL are potent inhibitors of CYP2C9 enzyme and are able to displace the Site I ligand warfarin from human serum albumin.","limitations":"in vitro only; no absorption or PK data"},"29755356":{"pmid":"29755356","title":"Anti-Parkinson Potential of Silymarin: Mechanistic Insight and Therapeutic Standing.","authors":"Ullah H, Khan H","journal":"Frontiers in pharmacology","year":"2018","volume":"9","issue":"","pages":"422","doi":"10.3389/fphar.2018.00422","url":"https://pubmed.ncbi.nlm.nih.gov/29755356/","species":"in_vitro","speciesRaw":"in vitro","design":"other (narrative review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review (Frontiers in Pharmacology, 2018) of silymarin in Parkinson's disease; not a primary absorption study. Abstract mentions low bioavailability (23-47%) as a secondary statement only.","conclusion":"NR","limitations":"review article, no primary data"},"30080294":{"pmid":"30080294","title":"Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases.","authors":"Abenavoli L, Izzo AA, Milić N, Cicala C, Santini A, Capasso R","journal":"Phytotherapy research : PTR","year":"2018","volume":"32","issue":"11","pages":"2202-2213","doi":"10.1002/ptr.6171","url":"https://pubmed.ncbi.nlm.nih.gov/30080294/","species":"human","speciesRaw":"human","design":"other (narrative review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review (Phytotherapy Research, 2018) of milk thistle chemistry, pharmacokinetics and liver-disease uses; not a primary study.","conclusion":"NR","limitations":"review article, no primary data"},"30108644":{"pmid":"30108644","title":"The Bioavailability and Pharmacokinetics of Silymarin SMEDDS Formulation Study in Healthy Thai Volunteers.","authors":"Sornsuvit C, Hongwiset D, Yotsawimonwat S, Toonkum M, Thongsawat S, Taesotikul W","journal":"Evidence-based complementary and alternative medicine : eCAM","year":"2018","volume":"2018","issue":"","pages":"1507834","doi":"10.1155/2018/1507834","url":"https://pubmed.ncbi.nlm.nih.gov/30108644/","species":"human","speciesRaw":"human","design":"single-arm","n":"12","status":"complete","statusNote":"Single-arm open-label PK of silymarin SMEDDS capsule; Table 4 compares with published values from other studies (not extracted as own arms).","conclusion":"It showed a fast absorption (tmax < 1 h) and high oral bioavailability (Cmax: 812.43 ng/ml, AUC0-t: 658.80 ng.h/ml).","limitations":"small n (12); single arm, no direct comparator (comparison is indirect with other published studies); industry funded; no absolute bioavailability measured; Table 1 contains typographical oddities"},"30176941":{"pmid":"30176941","title":"Chitosan-functionalized lipid-polymer hybrid nanoparticles for oral delivery of silymarin and enhanced lipid-lowering effect in NAFLD.","authors":"Liang J, Liu Y, Liu J, Li Z, Fan Q, Jiang Z, Yan F, Wang Z, Huang P, Feng N","journal":"Journal of nanobiotechnology","year":"2018","volume":"16","issue":"1","pages":"64","doi":"10.1186/s12951-018-0391-9","url":"https://pubmed.ncbi.nlm.nih.gov/30176941/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"partial","statusNote":"Preclinical formulation paper (rat PK of chitosan-lipid-polymer hybrid nanoparticles of silymarin); rat PK parameters (Cmax/AUC/Tmax) not printed, only relative-bioavailability fold values and Fig. 5. Mouse NAFLD pharmacodynamics not extracted.","conclusion":"CS-LPNs enhanced oral delivery of silymarin and exhibited a desirable lipid-lowering effect in a mouse model.","limitations":"values figure-only (Fig. 5); no Cmax/AUC/Tmax numbers printed; n inconsistent (6 vs 5); preclinical rat; no p-values for bioavailability fold changes"},"30416442":{"pmid":"30416442","title":"Baicalein Enhances the Oral Bioavailability and Hepatoprotective Effects of Silybin Through the Inhibition of Efflux Transporters BCRP and MRP2.","authors":"Xu P, Zhou H, Li YZ, Yuan ZW, Liu CX, Liu L, Xie Y","journal":"Frontiers in pharmacology","year":"2018","volume":"9","issue":"","pages":"1115","doi":"10.3389/fphar.2018.01115","url":"https://pubmed.ncbi.nlm.nih.gov/30416442/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"18 (3 groups of 6)","status":"complete","statusNote":"Silybin plus baicalein rat PK (Table 1), plus in vitro Caco-2/SCH efflux data. Hepatoprotection (CCl4) and non-silybin substrate MDCKII transporter data (Rho123, CDCFDA, pheophorbide A) not extracted.","conclusion":"efflux transporters play a critical role in the low bioavailability of silybin, while inhibition of breast cancer resistance protein (BCRP) and multi-drug resistance protein 2 (MRP2) by baicalein can significantly increase the absorption and bio-efficacy of silybin","limitations":"rat study only; small n (6/arm); baicalein dose and silybin dose both high (50 mg/kg); silybin vehicle not clearly stated in PK section; some values figure-only (Fig. 1, 2, 5)"},"30448315":{"pmid":"30448315","title":"Formulation and biopharmaceutical evaluation of supersaturatable self-nanoemulsifying drug delivery systems containing silymarin.","authors":"Tung NT, Tran CS, Nguyen HA, Nguyen TD, Chi SC, Pham DV, Bui QD, Ho XH","journal":"International journal of pharmaceutics","year":"2019","volume":"555","issue":"","pages":"63-76","doi":"10.1016/j.ijpharm.2018.11.036","url":"https://pubmed.ncbi.nlm.nih.gov/30448315/","species":"in_vitro","speciesRaw":"other animal (rabbit; also in vitro; mouse pharmacodynamics not extracted)","design":"parallel","n":"9 (4 Legalon + 5 S-SNEDDS)","status":"complete","statusNote":"Formulation paper: in vitro dissolution and rabbit PK (Legalon vs S-SNEDDS). Mouse CCl4 hepatoprotection data not extracted.","conclusion":"The combination of two techniques including SNEDDS and addition of 10% of Poloxamer 407 remarkably increased DE4h (88.28%) compared to the reference product (6.41%). The relative bioavailability of S-SNEDDS versus Legalon® was about 760%.","limitations":"small n (4 vs 5 rabbits); very low Legalon Cmax and AUC (near assay limit); variance is SE in PK; S-SNEDDS composition used in PK not itemized; relative bioavailability printed in Legalon column of Table 3"},"30502425":{"pmid":"30502425","title":"Design, optimization and in vitro-in vivo evaluation of smart nanocaged carrier delivery of multifunctional PEG-chitosan stabilized silybin nanocrystals.","authors":"Liu Y, Wang Y, Zhao J","journal":"International journal of biological macromolecules","year":"2019","volume":"124","issue":"","pages":"667-680","doi":"10.1016/j.ijbiomac.2018.11.258","url":"https://pubmed.ncbi.nlm.nih.gov/30502425/","species":"in_vitro","speciesRaw":"other animal (rabbit); also in vitro","design":"parallel","n":"9","status":"complete","statusNote":"Formulation (silybin nanocrystals) paper with IN VITRO dissolution and INTRAVENOUS rabbit PK of silybin (route is IV, not oral); PK on-target (silybin) but not an oral absorption study. Particle size, stability and lyophilization data not extracted.","conclusion":"the nanocaged nanocrystals technology with excellent stability, improved dissolution velocity and relative bioavailability was recommended as an efficient and feasible approach for water insoluble drugs delivery.","limitations":"intravenous administration, not oral absorption; n = 3 per group; values figure-only (Fig. 6F); AUC fold ratios inconsistent between Abstract, text and Table 5; control described as raw powder (Methods) vs solution (Table 5)"},"30635055":{"pmid":"30635055","title":"Superior silybin bioavailability of silybin-phosphatidylcholine complex in oily-medium soft-gel capsules versus conventional silymarin tablets in healthy volunteers.","authors":"Méndez-Sánchez N, Dibildox-Martinez M, Sosa-Noguera J, Sánchez-Medal R, Flores-Murrieta FJ","journal":"BMC pharmacology & toxicology","year":"2019","volume":"20","issue":"1","pages":"5","doi":"10.1186/s40360-018-0280-8","url":"https://pubmed.ncbi.nlm.nih.gov/30635055/","species":"human","speciesRaw":"human","design":"randomized crossover","n":"23 (24 enrolled)","status":"complete","statusNote":"","conclusion":"The silybin–phosphatidylcholine complex in oily-medium soft-gel capsules seems to provide superior bioavailability. However, clinical studies must be performed to demonstrate its clinical relevance in the treatment of liver diseases.","limitations":"doses not matched on silybin content (assayed 47.1 mg vs 29.5 mg); industry-linked (ITALMEX); single-dose, 8 h sampling; 90% CI ratios not printed; values figure-only (Fig. 1)"},"30643408":{"pmid":"30643408","title":"Co-delivery doxorubicin and silybin for anti-hepatoma via enhanced oral hepatic-targeted efficiency.","authors":"Li Y, Yang D, Wang Y, Li Z, Zhu C","journal":"International journal of nanomedicine","year":"2019","volume":"14","issue":"","pages":"301-315","doi":"10.2147/IJN.S187888","url":"https://pubmed.ncbi.nlm.nih.gov/30643408/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"partial","statusNote":"Oral PK in mice is reported for doxorubicin (DOX), not silybin; silybin appears as a co-loaded cardioprotective agent. Only a few silybin numbers (liver t1/2, encapsulation efficiency) are printed. DOX PK/biodistribution values are off-target analyte and not extracted as rows.","conclusion":"Concurrent administration of DOX and SLB via CA-LP provided a viable strategy to mitigate acute DOX-induced cardiotoxicity.","limitations":"silybin plasma PK not reported; PK dose and sampling times not stated; silybin data minimal (figure-only release); preclinical mouse"},"30668388":{"pmid":"30668388","title":"Piperine enhances the bioavailability of silybin via inhibition of efflux transporters BCRP and MRP2.","authors":"Bi X, Yuan Z, Qu B, Zhou H, Liu Z, Xie Y","journal":"Phytomedicine : international journal of phytotherapy and phytopharmacology","year":"2019","volume":"54","issue":"","pages":"98-108","doi":"10.1016/j.phymed.2018.09.217","url":"https://pubmed.ncbi.nlm.nih.gov/30668388/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"16","status":"complete","statusNote":"Rat PK of silybin with/without piperine plus in vitro transporter and metabolism studies; piperine PK (Supplemental Table 4/Fig. 2E) and CCl4 pharmacodynamics not extracted.","conclusion":"modulating these transporters by bioenhancer such as piperine could enhance the in vivo absorption of silybin, leading to more effective treatments.","limitations":"rat study; n = 8 per group; piperine dose inconsistent (10 vs 50 mg/kg); variance statistic described both as mean and geometric mean; some data figure-only"},"30766782":{"pmid":"30766782","title":"Supersaturated polymeric micelles for oral silybin delivery: the role of the Soluplus-PVPVA complex.","authors":"Zhu C, Gong S, Ding J, Yu M, Ahmad E, Feng Y, Gan Y","journal":"Acta pharmaceutica Sinica. B","year":"2019","volume":"9","issue":"1","pages":"107-117","doi":"10.1016/j.apsb.2018.09.004","url":"https://pubmed.ncbi.nlm.nih.gov/30766782/","species":"rodent","speciesRaw":"rodent","design":"parallel (4 groups, randomly divided); plus in vitro Caco-2 transport, solubility and supersaturation experiments","n":"NR","status":"complete","statusNote":"Animal (rat) oral PK of silybin formulations plus in vitro Caco-2/solubility/supersaturation work; Papp is figure-only.","conclusion":"In conclusion, the Soluplus–PVPVA complex is a potential SDDS for improving the bioavailability of hydrophobic drugs.","limitations":"rat study only, single dose level, n=6; pharmacokinetic matrix called plasma in Methods but blood in Table 2/Fig. 8 legends; SLB powder dose not separately stated; Caco-2 Papp and uptake values figure-only; dose basis not stated; no IV reference so absolute bioavailability not determined; formulation/polymer excipient study; not human"},"30795809":{"pmid":"30795809","title":"Correction to: Superior silybin bioavailability of silybin-phosphatidylcholine complex in oily-medium soft-gel capsules versus conventional silymarin tablets in healthy volunteers.","authors":"Méndez-Sánchez N, Dibildox-Martinez M, Sosa-Noguera J, Sánchez-Medal R, Flores-Murrieta FJ","journal":"BMC pharmacology & toxicology","year":"2019","volume":"20","issue":"1","pages":"14","doi":"10.1186/s40360-019-0290-1","url":"https://pubmed.ncbi.nlm.nih.gov/30795809/","species":"human","speciesRaw":"human","design":"other (correction notice)","n":"NR","status":"review/non-primary","statusNote":"Correction notice (author given/family name tagging error) for the original article BMC Pharmacol Toxicol 2019;20:5 on silybin-phosphatidylcholine vs silymarin tablets. Contains no data.","conclusion":"NR (correction notice)","limitations":"correction notice, no data"},"30904740":{"pmid":"30904740","title":"Development of a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for simultaneous determination of epigallocatechin-3-gallate, silibinin, and curcumin in plasma and different tissues after oral dosing of Protandim in rats and its application in pharmacokinetic and tissue distribution studies.","authors":"Song Y, Sun H, Xiao J, Wang F, Ding Y, Zhao J, Bai J, Cheng L, Gao K, Liu M, Guo Q, Zhang Y, Gao W, Jia Y, Wen A","journal":"Journal of pharmaceutical and biomedical analysis","year":"2019","volume":"170","issue":"","pages":"54-62","doi":"10.1016/j.jpba.2019.03.024","url":"https://pubmed.ncbi.nlm.nih.gov/30904740/","species":"rodent","speciesRaw":"rodent","design":"parallel (cohort A single dose, cohort B multiple dose; one group of rats per time point)","n":"NR","status":"complete","statusNote":"Rat PK/tissue distribution of silibinin after oral Protandim (multi-herbal product; also contains EGCG and curcumin, not extracted here because they are not the listed supplement). Validation tables not extracted (method validation, not absorption).","conclusion":"No analyte accumulated significantly after multiple doses at the intervals of 24 h. Epigallocatechin-3-gallate, silibinin, and curcumin were distributed mostly in the small intestine, and hardly in skin and brain, but moderately in the kidney, spleen, liver, lung, and heart.","limitations":"rat study, product (Protandim) not isolated silibinin; dose of SIL inferred only from stated content of product; SD/SEM not stated for Table 5/6 +/- values; plasma AUC and CL printed without variance; Tmax for multiple dose cohort sampling schedule not fully stated; figure-only concentration-time profiles; no IV comparator, CL units as printed L/Kg/h"},"30935093":{"pmid":"30935093","title":"Intestinal Permeability Study of Clinically Relevant Formulations of Silibinin in Caco-2 Cell Monolayers.","authors":"Pérez-Sánchez A, Cuyàs E, Ruiz-Torres V, Agulló-Chazarra L, Verdura S, González-Álvarez I, Bermejo M, Joven J, Micol V, Bosch-Barrera J, Menendez JA","journal":"International journal of molecular sciences","year":"2019","volume":"20","issue":"7","pages":"","doi":"10.3390/ijms20071606","url":"https://pubmed.ncbi.nlm.nih.gov/30935093/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro permeability)","n":"NR","status":"complete","statusNote":"In vitro Caco-2 permeability study; Papp values for several arms are figure-only.","conclusion":"Our approach predicted differential mechanisms of transport and blood–brain barrier permeabilities between the silibinin formulations tested.","limitations":"in vitro Caco-2 only; most Papp values figure-only; concentration of pure standard giving Papp not stated; Eurosil85 composition not described; no human PK data"},"31020859":{"pmid":"31020859","title":"Silymarin as a flavonoid-type P-glycoprotein inhibitor with impact on the pharmacokinetics of carbamazepine, oxcarbazepine and phenytoin in rats.","authors":"Ferreira A, Rodrigues M, Meirinho S, Fortuna A, Falcão A, Alves G","journal":"Drug and chemical toxicology","year":"2021","volume":"44","issue":"5","pages":"458-469","doi":"10.1080/01480545.2019.1601736","url":"https://pubmed.ncbi.nlm.nih.gov/31020859/","species":"rodent","speciesRaw":"rodent","design":"parallel (randomized groups: silymarin, verapamil positive control, vehicle)","n":"54 rats for systemic PK (6 per group per AED)","status":"off-target analyte","statusNote":"Silymarin (25 mg/kg, ip) was given as pretreatment (P-gp inhibitor); the measured analytes are the antiepileptic drugs carbamazepine, oxcarbazepine/licarbazepine and phenytoin (and metabolites) in rat plasma/brain. Silymarin/silybin concentrations were not measured, so no silymarin absorption data. Data sections not extracted.","conclusion":"Silymarin altered the pharmacokinetics of OXC, increasing its peak plasma concentration by 50% and its extent of systemic exposure by 41%, which had also impact on brain drug concentrations.","limitations":"off-target analyte; silymarin not quantified; intraperitoneal dosing"},"31035343":{"pmid":"31035343","title":"Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats.","authors":"Li Y, Wu Y, Li YJ, Meng L, Ding CY, Dong ZJ","journal":"Molecules (Basel, Switzerland)","year":"2019","volume":"24","issue":"9","pages":"","doi":"10.3390/molecules24091666","url":"https://pubmed.ncbi.nlm.nih.gov/31035343/","species":"rodent","speciesRaw":"rodent","design":"parallel (36 rats, six groups of six: SV 20/40/80 mg/kg with or without silymarin)","n":"36","status":"off-target analyte","statusNote":"Herb-drug interaction: silymarin (45 mg/kg oral, 7 days) was the perpetrator; measured analytes are simvastatin and simvastatin acid in rat plasma. Silymarin/silybin concentrations were not measured, so no silymarin absorption data. Data sections not extracted.","conclusion":"as the plasma concentration of SVA was found to increase when SV was co-administered with silymarin, the possibility of pharmacokinetic interactions between silymarin and SV should be considered to avoid potential adverse effects.","limitations":"off-target analyte; silymarin not quantified"},"31047898":{"pmid":"31047898","title":"Silymarin protects against radiocontrast-induced nephropathy in mice.","authors":"de Souza Santos V, Peters B, Côco LZ, Alves GM, de Assis ALEM, Nogueira BV, Meyrelles SS, Porto ML, Vasquez EC, Campagnaro BP, Pereira TMC","journal":"Life sciences","year":"2019","volume":"228","issue":"","pages":"305-315","doi":"10.1016/j.lfs.2019.04.061","url":"https://pubmed.ncbi.nlm.nih.gov/31047898/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"not absorption-related","statusNote":"Efficacy/pharmacology study of oral silymarin (50, 200, 300 mg/kg, 5 days) against radiocontrast-induced nephropathy in mice (renal function, oxidative stress, apoptosis, histology). No silymarin/silybin concentration or other PK/absorption measurement.","conclusion":"In summary, the present study demonstrates for the first time that silymarin decreases systemic and renal oxidative damage, preserving renal function and morphological architecture under exposure to a radiocontrast agent in mice.","limitations":"not an absorption/PK study"},"31052197":{"pmid":"31052197","title":"Formulation of Nanomicelles to Improve the Solubility and the Oral Absorption of Silymarin.","authors":"Piazzini V, D'Ambrosio M, Luceri C, Cinci L, Landucci E, Bilia AR, Bergonzi MC","journal":"Molecules (Basel, Switzerland)","year":"2019","volume":"24","issue":"9","pages":"","doi":"10.3390/molecules24091688","url":"https://pubmed.ncbi.nlm.nih.gov/31052197/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation characterization)","n":"NR","status":"complete","statusNote":"In vitro formulation study (solubility, release, PAMPA, Caco-2); no animal or human PK. PAMPA Pe values are figure-only.","conclusion":"PAMPA demonstrated that PNM and MNM enhanced the passive diffusion of SLM. Based on the cellular results, nanomicelles have a significant inhibitory effect on the P-gp-mediated efflux of SLM, and MNM increased SLM permeability through Caco-2 cells' monolayer compared to unformulated extract and PNM.","limitations":"in vitro only; PAMPA Pe values figure-only; ± type (SD/SEM) not stated for release values; free-SLM AP-BL not detected so no ratio; Caco-2 transport limited by 12 h exposure and cytotoxicity at lower dilution"},"31181687":{"pmid":"31181687","title":"Formulation Strategies for Enhancing the Bioavailability of Silymarin: The State of the Art.","authors":"Di Costanzo A, Angelico R","journal":"Molecules (Basel, Switzerland)","year":"2019","volume":"24","issue":"11","pages":"","doi":"10.3390/molecules24112155","url":"https://pubmed.ncbi.nlm.nih.gov/31181687/","species":"in_vitro","speciesRaw":"other animal (review of in vitro, animal and human studies)","design":"other (narrative review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review of formulation strategies for silymarin bioavailability (Molecules 2019;24:2155); secondary source, no original data extracted. Underlying primary studies should be extracted from their own papers.","conclusion":"The purpose of this study is to review the different nanostructured systems available in literature as delivery strategies to improve the absorption and bioavailability of silymarin.","limitations":"review article, secondary data"},"31185663":{"pmid":"31185663","title":"A Simple HPLC Method for the Quantitative Determination of Silybin in Rat Plasma: Application to a Comparative Pharmacokinetic Study on Commercial Silymarin Products.","authors":"Ha ES, Han DG, Seo SW, Kim JM, Lee SK, Sim WY, Yoon IS, Kim MS","journal":"Molecules (Basel, Switzerland)","year":"2019","volume":"24","issue":"11","pages":"","doi":"10.3390/molecules24112180","url":"https://pubmed.ncbi.nlm.nih.gov/31185663/","species":"rodent","speciesRaw":"rodent","design":"parallel (randomly divided into four groups)","n":"NR","status":"complete","statusNote":"Rat comparative PK of four commercial silymarin products (silybin measured). Method validation tables not extracted.","conclusion":"The comparative pharmacokinetic study on commercial silymarin products revealed that product #4 significantly enhanced the relative oral bioavailability of SBN compared to product #1–3.","limitations":"rat study, n=5 per group; products unnamed, composition/formulation not described; no IV reference so absolute bioavailability not determined; Tmax sampling resolution coarse (2-30 min); profiles figure-only"},"31207432":{"pmid":"31207432","title":"Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats.","authors":"Kumar N, Rai A, Reddy ND, Shenoy RR, Mudgal J, Bansal P, Mudgal PP, Arumugam K, Udupa N, Sharma N, Rao CM","journal":"Pharmacological reports : PR","year":"2019","volume":"71","issue":"4","pages":"703-712","doi":"10.1016/j.pharep.2019.03.013","url":"https://pubmed.ncbi.nlm.nih.gov/31207432/","species":"rodent","speciesRaw":"rodent","design":"other (animal formulation comparison; in vitro release, cell assays, hepatoprotection and PK sub-studies)","n":"12 (PK study)","status":"complete","statusNote":"Rat PK of silymarin suspension vs conventional liposomes (alcohol-intoxicated Wistar rats) plus in vitro release at pH 1.2/6.8","conclusion":"Conventional and PEGylated liposomes of silymarin were found to be more efficacious as hepatoprotective against alcohol-induced hepatotoxicity by its free radical scavenging and anti-inflammatory effects. Conventional liposomes showed enhanced bioavailability compared to silymarin alone.","limitations":"rodent (alcohol-intoxicated) model; only 4 sampling timepoints up to 2 h; AUC0-inf extrapolated; no statistical test reported for PK comparison; PK only done for conventional liposomes; no absolute bioavailability; variance type SEM stated in table footnote"},"31340181":{"pmid":"31340181","title":"Nanotherapeutic silibinin: An insight of phytomedicine in healthcare reformation.","authors":"Takke A, Shende P","journal":"Nanomedicine : nanotechnology, biology, and medicine","year":"2019","volume":"21","issue":"","pages":"102057","doi":"10.1016/j.nano.2019.102057","url":"https://pubmed.ncbi.nlm.nih.gov/31340181/","species":"unclear","speciesRaw":"NR","design":"NR","n":"NR","status":"review/non-primary","statusNote":"Narrative review of silibinin nanoformulations (Nanomedicine 2019); no primary PK data","conclusion":"()","limitations":"review article, no primary data"},"31420525":{"pmid":"31420525","title":"A Pharmacokinetic Natural Product-Disease-Drug Interaction: A Double Hit of Silymarin and Nonalcoholic Steatohepatitis on Hepatic Transporters in a Rat Model.","authors":"Montonye ML, Tian DD, Arman T, Lynch KD, Hagenbuch B, Paine MF, Clarke JD","journal":"The Journal of pharmacology and experimental therapeutics","year":"2019","volume":"371","issue":"2","pages":"385-393","doi":"10.1124/jpet.119.260489","url":"https://pubmed.ncbi.nlm.nih.gov/31420525/","species":"rodent","speciesRaw":"rodent","design":"other (animal PK; 2x2 diet x silymarin/vehicle, IV pitavastatin probe)","n":"16 rats purchased","status":"complete","statusNote":"On-target silymarin flavonolignan PK after IV dosing (10 mg/kg) in control vs NASH rats; pitavastatin (probe drug) outcomes not extracted as rows (off-target analyte), summarised under interactions","conclusion":"This double hit of NASH and silymarin on hepatic uptake transporters is another example of a multifactorial pharmacokinetic interaction that may have a greater impact on drug disposition than each hit alone.","limitations":"IV route only; no oral absorption data; n=4 rats per group; rodent MCD-diet NASH model; dose basis (silymarin extract mg/kg) not elemental flavonolignan; several values figure-only (Fig. 1, Fig. 2); fed/fasted status NR"},"31615114":{"pmid":"31615114","title":"Metabolism, Transport and Drug-Drug Interactions of Silymarin.","authors":"Xie Y, Zhang D, Zhang J, Yuan J","journal":"Molecules (Basel, Switzerland)","year":"2019","volume":"24","issue":"20","pages":"","doi":"10.3390/molecules24203693","url":"https://pubmed.ncbi.nlm.nih.gov/31615114/","species":"unclear","speciesRaw":"NR","design":"NR","n":"NR","status":"review/non-primary","statusNote":"Narrative review of silymarin metabolism, transport and drug-drug interactions (Molecules 2019); no primary PK data","conclusion":"()","limitations":"review article, no primary data"},"31706011":{"pmid":"31706011","title":"Combinational applicaton of silybin and tangeretin attenuates the progression of non-alcoholic steatohepatitis (NASH) in mice via modulating lipid metabolism.","authors":"Suguro R, Pang XC, Yuan ZW, Chen SY, Zhu YZ, Xie Y","journal":"Pharmacological research","year":"2020","volume":"151","issue":"","pages":"104519","doi":"10.1016/j.phrs.2019.104519","url":"https://pubmed.ncbi.nlm.nih.gov/31706011/","species":"rodent","speciesRaw":"rodent","design":"parallel (8 groups) animal efficacy study","n":"NR","status":"partial","statusNote":"Efficacy study in MCD-diet NASH mice; silybin plasma/liver concentrations with/without tangeretin are figure-only (Fig. 4), text gives only approximate fold change","conclusion":"In sum, we demonstrated that TG could enhance the therapeutic effect of SB against NASH possibly through regulating the oxidative stress, inflammatory responses, and lipid metabolism as well as enhancing bioavailability.","limitations":"silybin concentrations figure-only (Fig. 4); single timepoint (2 h post last dose), no PK parameters; mouse NASH model; dosing frequency not captured; SB-TG-H dose inconsistent between Methods and Fig. 1 legend; dose basis NR"},"31715362":{"pmid":"31715362","title":"Nanostructured lipid carriers for oral delivery of silymarin: Improving its absorption and in vivo efficacy in type 2 diabetes and metabolic syndrome model.","authors":"Piazzini V, Micheli L, Luceri C, D'Ambrosio M, Cinci L, Ghelardini C, Bilia AR, Di Cesare Mannelli L, Bergonzi MC","journal":"International journal of pharmaceutics","year":"2019","volume":"572","issue":"","pages":"118838","doi":"10.1016/j.ijpharm.2019.118838","url":"https://pubmed.ncbi.nlm.nih.gov/31715362/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation study plus mouse efficacy)","n":"NR","status":"partial","statusNote":"Only in vitro absorption-related data (PAMPA permeability, release) are numeric; no pharmacokinetic/plasma data; mouse part is efficacy only (glucose, lipids, pain) and not extracted; Caco-2 Papp is for the FITC probe in NLCs, not silymarin","conclusion":"This study demonstrates the importance of the nanocarriers in increasing the solubility and intestinal permeability of SLM.","limitations":"in vitro permeability only, no PK data; no unit or variance type printed next to PAMPA Pe values; release timepoints for SGF/SIF values NR; mouse part efficacy only; Caco-2 data are for FITC probe not silymarin"},"31923602":{"pmid":"31923602","title":"Phytosome-nanosuspensions for silybin-phospholipid complex with increased bioavailability and hepatoprotection efficacy.","authors":"Chi C, Zhang C, Liu Y, Nie H, Zhou J, Ding Y","journal":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences","year":"2020","volume":"144","issue":"","pages":"105212","doi":"10.1016/j.ejps.2020.105212","url":"https://pubmed.ncbi.nlm.nih.gov/31923602/","species":"rodent","speciesRaw":"rodent","design":"parallel (three groups, randomly divided)","n":"NR","status":"complete","statusNote":"Rat PK of silybin phytosome-nanosuspension (SPCs-NPs) vs SPCs physical mixture vs silybin physical mixture; Cmax only in figure; dissolution values for SPCs-NPs in text","conclusion":"Overall, the interesting finding of this study suggested that SPCs-NPs could be applied as a promising formulation for a higher drug bioavailability and better hepatoprotection efficacy.","limitations":"rodent study, n=5 per group; Cmax figure-only; no IV reference, no absolute bioavailability; silybin control is a physical mixture with phospholipid/excipients, not pure silybin alone (despite text calling it pure silybin); text/table CL inconsistency; dissolution comparators numeric values figure-only"},"32337654":{"pmid":"32337654","title":"Evaluation of Mogroside V as a Promising Carrier in Drug Delivery: Improving the Bioavailability and Liver Distribution of Silybin.","authors":"Luo Y, Gong C, Wei M, Chen Y, Song T, Wu C, Mo L, Zhang J","journal":"AAPS PharmSciTech","year":"2020","volume":"21","issue":"4","pages":"123","doi":"10.1208/s12249-020-01645-9","url":"https://pubmed.ncbi.nlm.nih.gov/32337654/","species":"rodent","speciesRaw":"rodent","design":"parallel (two groups) animal studies","n":"10 rats; 18 mice","status":"complete","statusNote":"Rat PK and mouse tissue distribution of silybin (SLY) solid dispersion with mogroside V (MOG-V SDPs) vs pure SLY; solubility and dissolution","conclusion":"Thus, MOG-V may have the applicability to serve as an ideal excipient for solubilization or as a novel liver targeting carrier for the delivery of SLY.","limitations":"rodent only; variance type (SD/SEM) not stated; n=5 rats, n=3 mice per timepoint; no IV reference; SDP ratio used in PK not explicit; Table II CL/F unit L/min/kg as printed"},"32473632":{"pmid":"32473632","title":"Functional oral nanoparticles for delivering silibinin and cryptotanshinone against breast cancer lung metastasis.","authors":"Liu Y, Xie X, Hou X, Shen J, Shi J, Chen H, He Y, Wang Z, Feng N","journal":"Journal of nanobiotechnology","year":"2020","volume":"18","issue":"1","pages":"83","doi":"10.1186/s12951-020-00638-x","url":"https://pubmed.ncbi.nlm.nih.gov/32473632/","species":"rodent","speciesRaw":"rodent","design":"parallel (four groups, randomly assigned)","n":"20 (4 groups of 5)","status":"partial","statusNote":"Rat oral PK of silibinin (SLB) co-loaded with cryptotanshinone in nanoparticles; only a few PK values are printed in the main text (full PK Tables S1/S2 are in supplementary file not in the PDF); concentration-time profiles are figure-only","conclusion":"Silibinin- and cryptotanshinone-co-loaded pW-LPNs efficiently penetrate intestinal barriers, thereby enhancing the oral bioavailability of the drug loads.","limitations":"PK parameter tables are supplementary (Additional file 1), not in PDF; AUC interval not stated; Cmax/Tmax not in main text; rat only, n=5; co-loaded with cryptotanshinone; SLB total after glucuronidase; ratio comparators described as 'the suspensions'"},"32654568":{"pmid":"32654568","title":"Silymarin loaded floating polymer(s) microspheres: characterization, in-vitro/in-vivo evaluation.","authors":"Ramadan AA, Elbakry AM, Sarhan HA, Ali SH","journal":"Pharmaceutical development and technology","year":"2020","volume":"25","issue":"9","pages":"1081-1089","doi":"10.1080/10837450.2020.1795192","url":"https://pubmed.ncbi.nlm.nih.gov/32654568/","species":"other_animal","speciesRaw":"other animal (New Zealand albino rabbit)","design":"parallel (described as 'parallel group study' / 'bio-equivalence study')","n":"6","status":"complete","statusNote":"Rabbit PK (silybin) of floating silymarin microspheres F24 vs commercial capsule (Silymarin plus); in vitro formulation characterization (buoyancy, release, stability) not extracted","conclusion":"Formulation of silymarin microspheres using HPMC, EC and blend of them was a successful trial.","limitations":"rabbit study, n=6 per group, single dose; variance type and statistic type not stated; no p-values printed; AUC0-24 and AUC0-∞ internally inconsistent in Table 10 (AUC0-24 9119.8 vs AUC0-∞ 9119; AUC24-∞ 1.755) as printed; design (parallel vs six rabbits total) unclear; dose basis NR"},"32877720":{"pmid":"32877720","title":"The food plant Silybum marianum (L.) Gaertn.: Phytochemistry, Ethnopharmacology and clinical evidence.","authors":"Marmouzi I, Bouyahya A, Ezzat SM, El Jemli M, Kharbach M","journal":"Journal of ethnopharmacology","year":"2021","volume":"265","issue":"","pages":"113303","doi":"10.1016/j.jep.2020.113303","url":"https://pubmed.ncbi.nlm.nih.gov/32877720/","species":"human","speciesRaw":"human","design":"other (narrative review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review of Silybum marianum phytochemistry, ethnopharmacology and clinical evidence; no primary absorption data extracted.","conclusion":"few studies have discussed its metabolism, pharmacokinetics and bioavailability, so that all future studies on S. marianum should focus on such areas.","limitations":"review article, not a primary study"},"33237069":{"pmid":"33237069","title":"Hydrophilic co-assemblies of two hydrophobic biomolecules improving the bioavailability of silybin.","authors":"He J , Chen Z , Gu Y , Li Y , Wang R , Gao Y , Feng W , Wang T","journal":"Food & function","year":"2020","volume":"11","issue":"12","pages":"10828-10838","doi":"10.1039/d0fo01882a","url":"https://pubmed.ncbi.nlm.nih.gov/33237069/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation characterisation and cell assays)","n":"NR","status":"partial","statusNote":"In vitro formulation paper (HepG-2 cell assays); no PK. 'Bioavailability' is inferred from cell cytotoxicity/apoptosis and cell internalisation, mostly shown in figures only.","conclusion":"Moreover, the encapsulation effectively improved the bioavailability of silybin by up to 50%.","limitations":"in vitro cell model only; no PK or intestinal absorption data; 'bioavailability' inferred from cytotoxicity/apoptosis; key values figure-only"},"33246779":{"pmid":"33246779","title":"Mucoadhesive nanocrystal-in-microspheres with high drug loading capacity for bioavailability enhancement of silybin.","authors":"Wang Y, Li H, Wang L, Han J, Yang Y, Fu T, Qiao H, Wang Z, Li J","journal":"Colloids and surfaces. B, Biointerfaces","year":"2021","volume":"198","issue":"","pages":"111461","doi":"10.1016/j.colsurfb.2020.111461","url":"https://pubmed.ncbi.nlm.nih.gov/33246779/","species":"rodent","speciesRaw":"rodent","design":"parallel (4 formulation groups)","n":"NR","status":"complete","statusNote":"Rat PK of silybin formulations plus in vitro release and ex vivo mucoadhesion; no human data.","conclusion":"The current study demonstrates that the developed delivery vehicle can enhance the bioavailability of SB by increasing its dissolution percentage as well as through extending retention time in the GI tract, and achieve high drug loading capacity.","limitations":"rat study, single dose, n = 6; dose reported inconsistently (35 vs 100 mg/kg); Cmax/AUC/MRT units partly unclear in Table 3; no human data"},"33257158":{"pmid":"33257158","title":"Amorphous silibinin nanoparticles loaded into porous starch to enhance remarkably its solubility and bioavailability in vivo.","authors":"Wu W, Wang L, Wang S","journal":"Colloids and surfaces. B, Biointerfaces","year":"2021","volume":"198","issue":"","pages":"111474","doi":"10.1016/j.colsurfb.2020.111474","url":"https://pubmed.ncbi.nlm.nih.gov/33257158/","species":"rodent","speciesRaw":"rodent","design":"parallel (3 formulation groups, randomised)","n":"18","status":"complete","statusNote":"Rat oral PK of silibinin formulations plus in vitro solubility/dissolution; no human data.","conclusion":"the SNPS might prove to be a preferred alternative to free SLB a formulation for SLB delivery in clinical treatment.","limitations":"rat study, single dose; n per group not stated; variance type and statistical methods not stated; significance claimed without p-values; text calls PK two-compartment model"},"33447529":{"pmid":"33447529","title":"Chronic Liver Disease and Silymarin: A Biochemical and Clinical Review.","authors":"Tighe SP, Akhtar D, Iqbal U, Ahmed A","journal":"Journal of clinical and translational hepatology","year":"2020","volume":"8","issue":"4","pages":"454-458","doi":"10.14218/JCTH.2020.00012","url":"https://pubmed.ncbi.nlm.nih.gov/33447529/","species":"human","speciesRaw":"human","design":"other (narrative review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review (J Clin Transl Hepatol) of silymarin in chronic liver disease; no primary absorption data extracted.","conclusion":"the overall efficacy of silymarin remains unclear and more research is warranted to better elucidate the role of silymarin in CLD, specifically regarding its anti-inflammatory effects.","limitations":"review article, not a primary study"},"33587317":{"pmid":"33587317","title":"Systematic review of pharmacokinetics and potential pharmacokinetic interactions of flavonolignans from silymarin.","authors":"Tvrdý V, Pourová J, Jirkovský E, Křen V, Valentová K, Mladěnka P","journal":"Medicinal research reviews","year":"2021","volume":"41","issue":"4","pages":"2195-2246","doi":"10.1002/med.21791","url":"https://pubmed.ncbi.nlm.nih.gov/33587317/","species":"human","speciesRaw":"human","design":"other (systematic review)","n":"NR","status":"review/non-primary","statusNote":"Systematic review of published pharmacokinetics and PK interactions of silymarin flavonolignans; secondary source, no primary data extracted.","conclusion":"NR","limitations":"review article, not a primary study"},"33587330":{"pmid":"33587330","title":"Hepatic organic anion transporting polypeptides mediate disposition of milk thistle flavonolignans and pharmacokinetic silymarin-drug interactions.","authors":"Lynch KD, Montonye ML, Tian DD, Arman T, Oyanna VO, Bechtold BJ, Graf TN, Oberlies NH, Paine MF, Clarke JD","journal":"Phytotherapy research : PTR","year":"2021","volume":"35","issue":"6","pages":"3286-3297","doi":"10.1002/ptr.7049","url":"https://pubmed.ncbi.nlm.nih.gov/33587330/","species":"rodent","speciesRaw":"rodent","design":"parallel (control vs NASH, vehicle vs silymarin); plus in vitro transporter experiments","n":"26","status":"complete","statusNote":"Rat PK of oral silymarin flavonolignans (control vs NASH) with pitavastatin interaction, plus in vitro OATP substrate/inhibition assays. Animal/in vitro, not human.","conclusion":"OATPs/Oatps transport flavonolignans and are important mediators of pharmacokinetic silymarin-drug interactions. Consuming silymarin doses at or above 700 mg may precipitate pharmacokinetic interactions with OATP drug substrates and place patients at risk for adverse drug reactions.","limitations":"rodent model, single dose, small n; silymarin dose basis (500 mg/kg) not given as flavonolignan content in this paper; some Table 1 analytes based on 3-4 animals; no randomization or blinding; interaction and transporter findings only partly relevant to absorption"},"33616078":{"pmid":"33616078","title":"Improving silymarin oral bioavailability using silica-installed redox nanoparticle to suppress inflammatory bowel disease.","authors":"Nguyen TT, Trinh NT, Tran HN, Tran HT, Le PQ, Ngo DN, Tran-Van H, Van Vo T, Vong LB, Nagasaki Y","journal":"Journal of controlled release : official journal of the Controlled Release Society","year":"2021","volume":"331","issue":"","pages":"515-524","doi":"10.1016/j.jconrel.2020.10.042","url":"https://pubmed.ncbi.nlm.nih.gov/33616078/","species":"rodent","speciesRaw":"rodent","design":"parallel (free silymarin vs SM@siRNP)","n":"NR","status":"partial","statusNote":"Mouse oral PK of silymarin vs silymarin-loaded nanoparticle; plasma and colon PK data (AUC, concentration-time) are in Fig. 4 only, no numeric values in text/tables. Also in vitro antioxidant/anti-inflammatory and DSS colitis efficacy work (not extracted).","conclusion":"The siRNP efficiently encapsulated silymarin to improve the solubility and bioavailability of silymarin.","limitations":"PK values are figure-only; n = 3 per group; single dose in healthy mice (PK) vs colitis model for efficacy; sampling times and AUC interval not stated in text"},"33706132":{"pmid":"33706132","title":"Interaction of silymarin components and their sulfate metabolites with human serum albumin and cytochrome P450 (2C9, 2C19, 2D6, and 3A4) enzymes.","authors":"Faisal Z, Mohos V, Fliszár-Nyúl E, Valentová K, Káňová K, Lemli B, Kunsági-Máté S, Poór M","journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","year":"2021","volume":"138","issue":"","pages":"111459","doi":"10.1016/j.biopha.2021.111459","url":"https://pubmed.ncbi.nlm.nih.gov/33706132/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro binding and enzyme inhibition)","n":"NR","status":"not absorption-related","statusNote":"In vitro study of silymarin flavonolignans and their sulfate metabolites binding to human serum albumin (logKSV, logK; Table 1) and inhibiting CYP2C9/2C19/2D6/3A4 (IC50; Table 2). No absorption, bioavailability or plasma PK data; data sections skipped per rule 10. Reviewer may wish to re-classify as a PK-interaction paper.","conclusion":"the simultaneous administration of high dose silymarin with medications should be carefully considered, because milk thistle flavonolignans and/or their sulfate metabolites may interfere with drug therapy.","limitations":"in vitro only; no absorption data"},"33925040":{"pmid":"33925040","title":"Enhanced Bioavailability and Efficacy of Silymarin Solid Dispersion in Rats with Acetaminophen-Induced Hepatotoxicity.","authors":"Song IS, Nam SJ, Jeon JH, Park SJ, Choi MK","journal":"Pharmaceutics","year":"2021","volume":"13","issue":"5","pages":"","doi":"10.3390/pharmaceutics13050628","url":"https://pubmed.ncbi.nlm.nih.gov/33925040/","species":"rodent","speciesRaw":"rodent","design":"parallel (silymarin vs silymarin-SD; single and repeated dose)","n":"NR","status":"complete","statusNote":"Rat study: silybin PK after single and repeated oral silymarin vs silymarin-TPGS solid dispersion in APAP-hepatotoxic rats, liver distribution, ex vivo jejunal permeability, solubility. Efficacy (ALT/AST etc.) not extracted.","conclusion":"the solid dispersion formulation of silymarin-TPGS may be used to increase solubility and intestinal permeability; therefore, multiple silymarin-SD treatment (at a dose of 20 mg/kg as silybin) exhibited higher plasma concentrations and better hepatoprotective properties than the treatment of silymarin alone in APAP-induced hepatotoxic rats.","limitations":"rodent study with hepatotoxic (APAP) model, n = 4 per group; several values figure-only; internal inconsistencies in fold values; industry-independent but single dose level"},"34172076":{"pmid":"34172076","title":"Correction to: Superior silybin bioavailability of silybin-phosphatidylcholine complex in oily-medium soft-gel capsules versus conventional silymarin tablets in healthy volunteers.","authors":"Méndez-Sánchez N, Dibildox-Martinez M, Sosa-Noguera J, Sánchez-Medal R, Flores-Murrieta FJ","journal":"BMC pharmacology & toxicology","year":"2021","volume":"22","issue":"1","pages":"37","doi":"10.1186/s40360-021-00500-2","url":"https://pubmed.ncbi.nlm.nih.gov/34172076/","species":"unclear","speciesRaw":"NR","design":"NR","n":"NR","status":"review/non-primary","statusNote":"Published erratum (1 page) correcting a unit in the Results sentence of Méndez-Sánchez et al. BMC Pharmacol Toxicol 2019;20:5 (doi 10.1186/s40360-018-0280-8). The original article, not this notice, holds the data. The correction states SIB peak plasma concentrations were 207.1 ng/L for SPC and 12.6 ng/L for SM tablets (original printed mg/L).","conclusion":"()","limitations":"correction notice only"},"34285784":{"pmid":"34285784","title":"Liver Protection Mechanism and Absorption Promotion Technology of Silybin Based on Intelligent Medical Analysis.","authors":"Yan B, Zhang C","journal":"Journal of healthcare engineering","year":"2021","volume":"2021","issue":"","pages":"9968016","doi":"10.1155/2021/9968016","url":"https://pubmed.ncbi.nlm.nih.gov/34285784/","species":"unclear","speciesRaw":"NR","design":"NR","n":"NR","status":"not absorption-related","statusNote":"Retracted article (Hindawi retraction notice on PDF p.1: peer review compromised, retracted Nov 2022) bundled with the original paper. The paper reports silybin hepatoprotection in CCl4 mice (serum ALT/AST, NF-kB, NO, mortality); no silybin concentration, PK or bioavailability data. 'Absorption promotion' in the title refers to a small-intestinal food retention rate in the model group (p = 0.024), not absorption of silybin.","conclusion":"()","limitations":"retracted publication; no PK data"},"34695708":{"pmid":"34695708","title":"Investigation on the solid-phase synthesis of silybin prodrugs and their timed-release.","authors":"Romanucci V, Giordano M, Pagano R, Zimbone S, Giuffrida ML, Milardi D, Zarrelli A, Di Fabio G","journal":"Bioorganic & medicinal chemistry","year":"2021","volume":"50","issue":"","pages":"116478","doi":"10.1016/j.bmc.2021.116478","url":"https://pubmed.ncbi.nlm.nih.gov/34695708/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro chemical/enzymatic stability study)","n":"NR","status":"partial","statusNote":"In vitro chemistry study: solid-phase synthesis of silybin ribonucleotide prodrugs with in vitro stability, solubility and RNase A release kinetics. No in vivo absorption/PK. Extracted release half-lives, solubility and stability (parameter 'other'); DPPH, yields and cytotoxicity not extracted as unrelated.","conclusion":"Uridine-silybin prodrugs were quickly cleaved by RNase A, releasing the active silybin drugs even at low RNase concentrations.","limitations":"in vitro only, no absorption or PK data; no variance reported for half-lives; sIF stability stated qualitatively (t1/2 much greater than 24 h); supplementary data not available"},"34944582":{"pmid":"34944582","title":"Preparation and Characterization of Silymarin-Conjugated Gold Nanoparticles with Enhanced Anti-Fibrotic Therapeutic Effects against Hepatic Fibrosis in Rats: Role of MicroRNAs as Molecular Targets.","authors":"Abdullah AS, El Sayed IET, El-Torgoman AMA, Alghamdi NA, Ullah S, Wageh S, Kamel MA","journal":"Biomedicines","year":"2021","volume":"9","issue":"12","pages":"","doi":"10.3390/biomedicines9121767","url":"https://pubmed.ncbi.nlm.nih.gov/34944582/","species":"in_vitro","speciesRaw":"in vitro","design":"other (formulation characterisation + in vitro release + in vivo pharmacodynamic rat study)","n":"30 rats (in vivo part)","status":"partial","statusNote":"Nanoparticle formulation paper. Extracted only entrapment/loading and in vitro silymarin release from silymarin-gold nanoparticles (SGNPs); the rat CCl4 study measures antifibrotic pharmacodynamics (liver enzymes, miRNAs, histology) and reports no silymarin concentration/PK data (authors state PK still to be investigated).","conclusion":"We successfully synthesized SIL-loaded GNPs (SGNPs) with sizes ranging from 16 up to 20 nm, entrapment efficiency 96%, and loading capacity 38.69%. The in vivo study indicated that the obtained nano-formulation of SIL boosts its anti-fibrotic effects.","limitations":"in vitro release only, no in vivo PK/absorption data; release data mostly figure-only; approximate (~) values in text; preparation used in release study not stated; no variance printed in text/tables for EE/LC"},"35061161":{"pmid":"35061161","title":"Prediction of CYP-mediated silybin A-losartan pharmacokinetic interactions using physiological based pharmacokinetic modeling.","authors":"Tanveer A, Hussain K, Tasneem H, Arif I, Rashid M, Abbas N, Shamim R, Shah PA, Bukhari NI","journal":"Journal of pharmacokinetics and pharmacodynamics","year":"2022","volume":"49","issue":"3","pages":"311-323","doi":"10.1007/s10928-022-09804-0","url":"https://pubmed.ncbi.nlm.nih.gov/35061161/","species":"human","speciesRaw":"human","design":"other (PBPK modelling/simulation)","n":"NR","status":"partial","statusNote":"In silico PBPK simulation study (PK-Sim): predicts silybin A PK (Table 4) and its CYP2C9-mediated interaction with losartan in three CYP2C9 genotypes. No new human/animal measurements; all 'predicted' values are model outputs. 'Observed' values listed are from cited clinical studies. Losartan (interaction victim) values are included as interaction results.","conclusion":"Silybin A changed the AUC and Cmax of losartan in a genotype-dependent manner. The pharmacokinetic interactions between silybin A and losartan were minor when concomitantly administered at normal doses in genotypes CYP2C9*1/*1 and CYP2C9*1/*3. However, moderate interaction was found in CYP2C9*1/*2 genotype.","limitations":"in silico simulation, not measured data; CYP2C9*1/*2 decrease unexplained and not clinically validated; losartan metabolite not modelled; model validated against digitised published profiles; internal inconsistencies in reported fold ratios and units"},"35214124":{"pmid":"35214124","title":"Hydroxypropyl-β-cyclodextrin Enhances Oral Absorption of Silymarin Nanoparticles Prepared Using PureNano™ Continuous Crystallizer.","authors":"Onodera R, Hayashi T, Motoyama K, Tahara K, Takeuchi H","journal":"Pharmaceutics","year":"2022","volume":"14","issue":"2","pages":"","doi":"10.3390/pharmaceutics14020394","url":"https://pubmed.ncbi.nlm.nih.gov/35214124/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation characterisation)","n":"NR","status":"partial","statusNote":"Pharmaceutics/in vitro mechanism study of silymarin nanoparticles (dissolution, solubility, Caco-2 permeability, contact angle). No new in vivo PK; only a cited prior rat result (3.3-fold AUC0-6h, 4.2-fold Cmax). Many values figure-only; particle size, contact angle, XRD and SEM not extracted.","conclusion":"We revealed that HP-β-CyD was a potential cryoprotectant in NP formulation using an SLM nano-suspension prepared by PureNano. SLM/HPMC/HP-β-CyD NPs showed good redispersion ability and rapid dissolution rate, probably due to the complex formation with SLM.","limitations":"in vitro only; most dissolution and permeability values figure-only; approximate values ('~', 'almost') in text; no phase II metabolism/bile excretion assessed; in vivo data only cited from previous paper"},"35300217":{"pmid":"35300217","title":"In vitro Dissolution Testing and Pharmacokinetic Studies of Silymarin Solid Dispersion After Oral Administration to Healthy Pigs.","authors":"Xu Y, Li J, He B, Feng T, Liang L, Huang X","journal":"Frontiers in veterinary science","year":"2022","volume":"9","issue":"","pages":"815198","doi":"10.3389/fvets.2022.815198","url":"https://pubmed.ncbi.nlm.nih.gov/35300217/","species":"other_animal","speciesRaw":"other animal (pig)","design":"parallel (randomized two groups) plus in vitro dissolution","n":"16","status":"complete","statusNote":"","conclusion":"The solid dispersion exhibited the higher Cmax and AUC compared to the premix, and that is consistent with in vitro dissolution data.","limitations":"pigs (13.7 kg) given silybin 50 mg/kg by gavage; not human; parallel groups of n=8; no IV reference so absolute bioavailability not assessed; sex and fasting status NR; Table 4 has no relative bioavailability row despite text citing it; solid dispersion and premix differ in excipients and silybin content"},"35300372":{"pmid":"35300372","title":"Synthesis of silymarin-selenium nanoparticle conjugate and examination of its biological activity in vitro.","authors":"Staroverov SA, Kozlov SV, Fomin AS, Gabalov KP, Khanadeev VA, Soldatov DA, Domnitsky IY, Dykman LA, Akchurin SV, Guliy OI","journal":"ADMET & DMPK","year":"2021","volume":"9","issue":"4","pages":"255-266","doi":"10.5599/admet.1023","url":"https://pubmed.ncbi.nlm.nih.gov/35300372/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro nanoparticle synthesis and cell assays)","n":"NR","status":"partial","statusNote":"In vitro nanoparticle conjugate paper (silymarin-selenium nanoparticles). Only quantitative silymarin item is the HPLC silymarin concentration of the conjugate; cell penetration of silymarin shown only by fluorescence microscopy images (qualitative, figures); remainder is cytotoxicity/MTT and dehydrogenase activity (not absorption). No PK.","conclusion":"Thus, SeNPs are promising for use as a Sil carrier and as protective antigens.","limitations":"in vitro only; cell penetration qualitative (images); no PK or quantitative uptake data; abstract/discussion claim increased bioavailability without a bioavailability measurement; no statistics beyond p-values for dehydrogenase activity"},"35460909":{"pmid":"35460909","title":"Preclinical validation of silibinin/albumin nanoparticles as an applicable system against acute liver injury.","authors":"Ding Y, Zhang S, Sun Z, Tong Z, Ge Y, Zhou L, Xu Q, Zhou H, Wang W","journal":"Acta biomaterialia","year":"2022","volume":"146","issue":"","pages":"385-395","doi":"10.1016/j.actbio.2022.04.021","url":"https://pubmed.ncbi.nlm.nih.gov/35460909/","species":"rodent","speciesRaw":"rodent","design":"other (preclinical formulation/biodistribution/efficacy study)","n":"NR","status":"partial","statusNote":"Silibinin/BSA nanoparticle paper dominated by hepatoprotection (APAP and LPS/D-GalN mouse and cell models). Absorption-relevant content is limited to in vitro release (text), i.v. biodistribution in mice (text statements only; numbers in Supplementary Fig. S8/Table S3, not available) and cited ratios from another study. Intravenous administration, not oral.","conclusion":"SIL/BSA nanoparticles were successfully prepared to enhance the liver availability of SIL. Both in vivo and in vitro, SIL/BSA nanoparticles exerted ideal hepatoprotective and antioxidant efficacy against acute liver injury, suggesting the promising future in clinical transfer.","limitations":"intravenous route, not oral absorption; PK/biodistribution numbers only in supplementary material (unavailable); no PK parameters (Cmax, AUC) reported in main text; n for biodistribution not stated; animal study"},"35560136":{"pmid":"35560136","title":"Lung cancer targeting efficiency of Silibinin loaded Poly Caprolactone /Pluronic F68 Inhalable nanoparticles: In vitro and In vivo study.","authors":"Patel P, Raval M, Manvar A, Airao V, Bhatt V, Shah P","journal":"PloS one","year":"2022","volume":"17","issue":"5","pages":"e0267257","doi":"10.1371/journal.pone.0267257","url":"https://pubmed.ncbi.nlm.nih.gov/35560136/","species":"rodent","speciesRaw":"rodent","design":"other (preclinical parallel-group rat PK, 3 groups)","n":"NR","status":"complete","statusNote":"Silibinin on-target: rat PK of SB solution (IV), SB-loaded PCL/Pluronic F68 NPs IV, and NPs by inhalation (micro-spray aerosolizer / modified powder inhaler). Preclinical nanoformulation study; in vitro release also reported.","conclusion":"SB loaded PCL/ Pluronic F68 nanoparticles were successfully prepared with good entrapment, smaller particle size along uniform spherical shape and good aerosolization behaviour.","limitations":"preclinical rat study; dose and n inconsistent within paper (1.8 vs 2.0 mg/kg; n=6 vs n=3 vs n=12); Tmax units not printed; no statistical tests reported for PK parameters; tissue biodistribution figure-only; abstract says >4-fold AUC rise vs IV, Table 5 AUCs are 587.31 vs 325.21 (ratio not stated)"},"35651070":{"pmid":"35651070","title":"A review of nanostructured delivery systems for the encapsulation, protection, and delivery of silymarin: An emerging nutraceutical.","authors":"Zhang Z, Li X, Sang S, McClements DJ, Chen L, Long J, Jiao A, Wang J, Jin Z, Qiu C","journal":"Food research international (Ottawa, Ont.)","year":"2022","volume":"156","issue":"","pages":"111314","doi":"10.1016/j.foodres.2022.111314","url":"https://pubmed.ncbi.nlm.nih.gov/35651070/","species":"other_animal","speciesRaw":"other animal (specify)","design":"other (review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review (PubMed type: Review) of nanostructured delivery systems for silymarin; no primary PK data extracted.","conclusion":"The encapsulation in edible nanocarriers can improve the bioavailability of silymarin by enhancing its water-dispersibility, inhibiting its degradation, and increasing its absorption.","limitations":"review article, secondary source"},"35708053":{"pmid":"35708053","title":"In-depth investigation of the Silymarin effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 and ledipasvir in rat plasma using LC-MS.","authors":"Aboras SI, Korany MA, El-Yazbi AF, Ragab MAA, Abdine HH","journal":"Biomedical chromatography : BMC","year":"2022","volume":"36","issue":"9","pages":"e5427","doi":"10.1002/bmc.5427","url":"https://pubmed.ncbi.nlm.nih.gov/35708053/","species":"rodent","speciesRaw":"rodent","design":"parallel (control vs + silymarin), 2 groups","n":"8","status":"off-target analyte","statusNote":"Silymarin was co-administered as a perpetrator; measured PK analytes are sofosbuvir, GS-331007 and ledipasvir (drug-interaction study). Silibinin B was quantified in the method validation but no silymarin/silibinin PK data are reported for the treated rats. Table 4 rows recorded for reference only.","conclusion":"SLY-induced inhibition of SFB and LED metabolism, which could be explained by SLY competitive inhibition of their hepatic uptake associated with a decreased SFB metabolism, appeared in the AUC of GS-331007.","limitations":"n = 4 per group; off-target analytes (not silymarin PK); silymarin plasma levels not reported; rat study; identical K/t1/2 printed for LED and GS-331007"},"35890088":{"pmid":"35890088","title":"Phytosomes as a Plausible Nano-Delivery System for Enhanced Oral Bioavailability and Improved Hepatoprotective Activity of Silymarin.","authors":"Shriram RG, Moin A, Alotaibi HF, Khafagy ES, Al Saqr A, Abu Lila AS, Charyulu RN","journal":"Pharmaceuticals (Basel, Switzerland)","year":"2022","volume":"15","issue":"7","pages":"","doi":"10.3390/ph15070790","url":"https://pubmed.ncbi.nlm.nih.gov/35890088/","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups, PK)","n":"NR","status":"complete","statusNote":"Rat oral PK of pure silymarin vs silymarin-phosphatidylcholine phytosomes (Table 5); plus in vitro solubility/dissolution. Hepatoprotective/antioxidant outcomes skipped as unrelated to absorption.","conclusion":"the optimized silymarin phytosomal formulation significantly improved silymarin oral bioavailability as evidenced by a ~6-fold increase in systemic bioavailability compared to pure silymarin.","limitations":"rat study; phytosome AUC0-t > AUC0-inf as printed; sampling to 12 h but AUC0-24h stated; relative bioavailability not tabulated; silymarin analyte (marker constituent) not specified; single-dose, no fed/fasted info"},"36178580":{"pmid":"36178580","title":"Enhanced bioavailability and hepatoprotective effect of silymarin by preparing silymarin-loaded solid dispersion formulation using freeze-drying method.","authors":"Lim DY, Pang M, Lee J, Lee J, Jeon JH, Park JH, Choi MK, Song IS","journal":"Archives of pharmacal research","year":"2022","volume":"45","issue":"10","pages":"743-760","doi":"10.1007/s12272-022-01407-0","url":"https://pubmed.ncbi.nlm.nih.gov/36178580/","species":"rodent","speciesRaw":"rodent","design":"parallel (3 groups per experiment), two separate experiments","n":"NR","status":"complete","statusNote":"Two rat PK experiments (Table 1, Table 2) plus in vitro permeability/solubility/dissolution; hepatoprotective ALT/AST/ALP results not extracted.","conclusion":"the silymarin-SD formulation improved silymarin BA by increasing its solubility, dissolution, and oral absorption via inhibiting silymarin efflux and silymarin glucuronidation in the intestine.","limitations":"n = 4 per group; rat study; dose inconsistency for Exp 2 (text 20 vs table 50 mg/kg); relative BA AUC interval not stated; Papp/solubility mostly figure-only; glucuronide quantified against silymarin curve"},"36343684":{"pmid":"36343684","title":"Inhibition of UGT1A1*1 and UGT1A1*6 catalyzed glucuronidation of SN-38 by silybins.","authors":"Li W, Chen YN, Chen YY, Wang Z, Wang Z, Jiang LL, Shi HC, Liu Y","journal":"Chemico-biological interactions","year":"2022","volume":"368","issue":"","pages":"110248","doi":"10.1016/j.cbi.2022.110248","url":"https://pubmed.ncbi.nlm.nih.gov/36343684/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro enzyme inhibition and DDI prediction)","n":"NR","status":"not absorption-related","statusNote":"In vitro enzyme-inhibition study (silybin A/B inhibition of recombinant UGT1A1*1/*6-catalysed SN-38 glucuronidation; IC50/Ki) with model-predicted herb-drug interaction ratios. No absorption/PK measurements by the authors; Table 2 reproduces literature plasma Cmax of silybins from other studies.","conclusion":"the coadministration of irinotecan and several milk thistle products might result into clinically significant drug interactions.","limitations":"no in vivo absorption data; Cmax values in Table 2 are taken from other studies (refs 7-11)"},"36381105":{"pmid":"36381105","title":"Preclinical Long-term Magnetic Resonance Imaging Study of Silymarin Liver-protective Effects.","authors":"Chae YJ, Heo H, Woo CW, Kim ST, Kwon JI, Choi MY, Sung YS, Kim KW, Kim JK, Choi Y, Woo DC","journal":"Journal of clinical and translational hepatology","year":"2022","volume":"10","issue":"6","pages":"1167-1175","doi":"10.14218/JCTH.2021.00499","url":"https://pubmed.ncbi.nlm.nih.gov/36381105/","species":"rodent","speciesRaw":"rodent","design":"other (preclinical efficacy, 3 groups)","n":"NR","status":"not absorption-related","statusNote":"Efficacy study: longitudinal MRI and serum/histology biomarkers of silymarin (100 mg/kg i.p., 3x/week) in thioacetamide-induced rat liver injury. No silymarin concentration, absorption or PK measurement; AUCtmax refers to Gd-EOB-DTPA MRI enhancement, not silymarin.","conclusion":"Silymarin had hepatoprotective effects on TAA-induced liver injury and demonstrated the usefulness of multiparametric MRI to evaluate efficacy in preclinical studies of liver drug development.","limitations":"no absorption/PK data"},"36475008":{"pmid":"36475008","title":"Retracted: Liver Protection Mechanism and Absorption Promotion Technology of Silybin Based on Intelligent Medical Analysis.","authors":"Engineering JOH","journal":"Journal of healthcare engineering","year":"2022","volume":"2022","issue":"","pages":"9816410","doi":"10.1155/2022/9816410","url":"https://pubmed.ncbi.nlm.nih.gov/36475008/","species":"in_vitro","speciesRaw":"in vitro","design":"other (retraction notice)","n":"NR","status":"review/non-primary","statusNote":"Retraction notice (1 page) for 'Liver Protection Mechanism and Absorption Promotion Technology of Silybin Based on Intelligent Medical Analysis' (Yan & Zhang, J Healthcare Eng 2021, 9968016), retracted because the peer review process was compromised. Not the original paper; no data.","conclusion":"The article was retracted due to concerns that the peer review process has been compromised.","limitations":"retracted source; the original article (vol 2021, ID 9968016) should not be used"},"36557984":{"pmid":"36557984","title":"Silymarin Protects against Acute Liver Injury Induced by Acetaminophen by Downregulating the Expression and Activity of the CYP2E1 Enzyme.","authors":"Yang W, Liang Z, Wen C, Jiang X, Wang L","journal":"Molecules (Basel, Switzerland)","year":"2022","volume":"27","issue":"24","pages":"","doi":"10.3390/molecules27248855","url":"https://pubmed.ncbi.nlm.nih.gov/36557984/","species":"rodent","speciesRaw":"rodent","design":"parallel (solvent control vs silymarin pretreatment)","n":"12","status":"off-target analyte","statusNote":"Silymarin used as CYP2E1 inhibitor/pretreatment; measured PK analytes are chlorzoxazone (probe) and its metabolite 6-OH-chlorzoxazone in rats (and APAP and its metabolites in mice). Silymarin plasma/liver concentrations are only in Supplementary Table S4 (not in PDF). Table 2/3 recorded for reference only.","conclusion":"The results of our study show that silymarin plays an important protective role in the early stage of acetaminophen-induced acute liver injury by reducing the activity and expression of CYP2E1, reducing the generation of toxic metabolites, and alleviating liver injury.","limitations":"off-target analytes; n = 6 per group; silymarin exposure data only in Supplementary Table S4; Fig. 3 labels say mice but study used rats"},"36719351":{"pmid":"36719351","title":"Albumin-Based Silibinin Nanocrystals Targeting Activated Hepatic Stellate Cells for Liver Fibrosis Therapy.","authors":"Luo S, Yang Y, Zhao T, Zhang R, Fang C, Li Y, Zhang Z, Gong T","journal":"ACS applied materials & interfaces","year":"2023","volume":"15","issue":"6","pages":"7747-7758","doi":"10.1021/acsami.2c19269","url":"https://pubmed.ncbi.nlm.nih.gov/36719351/","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups, PK), preclinical","n":"10 (PK)","status":"complete","statusNote":"Silibinin on-target; IV (tail vein) administration only, so no oral absorption data. Rat PK (Table 1), mouse biodistribution (figure/supplement only), in vitro release and cell uptake. Efficacy outcomes (ALT/AST, Sirius red) not extracted.","conclusion":"SLB-HSA NCs are capable of being a secure and efficient aHSCs-targeted drug delivery system for liver fibrosis therapy.","limitations":"intravenous route only (no oral absorption); rat PK n=5; no Cmax/Tmax reported; biodistribution values in figure/supplement only; bioavailability claim refers to i.v. exposure"},"36775115":{"pmid":"36775115","title":"Combinations of grape seed procyanidin extract and milk thistle silymarin extract against lung cancer - The role of MiR-663a and FHIT.","authors":"Mao JT, Xue B, Lu QY, Lundmark L, Burns W, Yang J, Lee RP, Glass J, Qualls C, Massie L","journal":"Life sciences","year":"2023","volume":"318","issue":"","pages":"121492","doi":"10.1016/j.lfs.2023.121492","url":"https://pubmed.ncbi.nlm.nih.gov/36775115/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"partial","statusNote":"Primarily an anticancer efficacy study; only absorption data is Table 2 (mouse plasma, single time point, no variance). Grape seed (LP) analytes in Table 2 (C, EC, ECG, M-C, M-EC, M-ECG, B1, B2) are not milk thistle and were not extracted.","conclusion":"We also demonstrated the systemic bioavailabilities of LP and siliphos by quantifying plasma GSE, MTE and their respective metabolites.","limitations":"single time point (8 weeks), time after last dose NR; no variance, n or statistic type reported for Table 2; mouse model; absorption secondary to anticancer aim; dose basis: siliphos 1000 mg/kg product (400 mg/kg silybin)"},"36985575":{"pmid":"36985575","title":"Preparation, Characterization and Evaluation of Flavonolignan Silymarin Effervescent Floating Matrix Tablets for Enhanced Oral Bioavailability.","authors":"Ahmad S, Khan JA, Kausar TN, Mahnashi MH, Alasiri A, Alqahtani AA, Alqahtani TS, Walbi IA, Alshehri OM, Elnoubi OA, Mahmood F, Sadiq A","journal":"Molecules (Basel, Switzerland)","year":"2023","volume":"28","issue":"6","pages":"","doi":"10.3390/molecules28062606","url":"https://pubmed.ncbi.nlm.nih.gov/36985575/","species":"in_vitro","speciesRaw":"other animal (albino rabbit); human volunteers only for ultrasound floating study; in vitro dissolution","design":"parallel","n":"NR","status":"complete","statusNote":"Formulation paper (floating matrix tablet) with a rabbit PK comparison vs a conventional capsule (Table 5) plus in vitro release and a 6-volunteer ultrasound gastric-retention study (no blood PK in humans).","conclusion":"The silymarin gastro-retentive formulation achieved an improved area under the curve, longer MRT, and longer half-life as compared to the conventional formulation in rabbits.","limitations":"single animal species (rabbit) with n=6 per group; variance type for +/- values not stated; dose unit inconsistent (mg/kg in Table 5 vs 200 mg in text); sampling times and half-life values not reported in text/tables; a single p<0.05 reported without per-parameter p-values; industry/other conflicts: none declared"},"37342048":{"pmid":"37342048","title":"In-silico, in-vitro and ex-vivo evidence of combining silymarin phytopharmaceutical with piperine, and fulvic acid for enhancing its solubility and permeability.","authors":"Ralli T, Saifi Z, Kumari A, Aeri V, Kohli K","journal":"Pharmaceutical development and technology","year":"2023","volume":"28","issue":"7","pages":"595-610","doi":"10.1080/10837450.2023.2227966","url":"https://pubmed.ncbi.nlm.nih.gov/37342048/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in silico + in vitro + ex vivo)","n":"NR","status":"partial","statusNote":"In-silico, in-vitro (dissolution/solubility) and ex-vivo rat gut sac study of silymarin phytopharmaceutical with piperine and fulvic acid; no in vivo PK. Docking and Lipinski data not extracted.","conclusion":"Thus, the use of described BEs had in turns increased the BA of SM and might have the probability of increasing the NAFLD activity.","limitations":"no in vivo PK; in vitro/ex vivo only; n=3 per condition; variance type not stated; comparator doses NR; Papp exponent printed without minus sign; abstract inconsistent with results; no p-values for release comparisons"},"37457888":{"pmid":"37457888","title":"Design, Synthesis and Biological Evaluation of Glycosylated Derivatives of Silibinin as Potential Anti-Tumor Agents.","authors":"Xi JJ, Cao Y, He RY, Zhang JK, Zhao YM, Tong Q, Bao JF, Dong YC, Zhuang RX, Huang JS, Chen Y, Liu SR","journal":"Drug design, development and therapy","year":"2023","volume":"17","issue":"","pages":"2063-2076","doi":"10.2147/DDDT.S404036","url":"https://pubmed.ncbi.nlm.nih.gov/37457888/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"partial","statusNote":"Medicinal-chemistry paper on synthetic glycosylated silibinin derivatives; absorption-relevant data are silibinin water solubility (literature value), mouse liver microsomal stability, and an intravenous mouse PK (silibinin vs derivative 15, i.v. only; no oral PK). Cytotoxicity/apoptosis/cell cycle not extracted.","conclusion":"All of results supported that the introduction of glycosyl in the 3-OH and 23-OH position of silibinin would be a feasible strategy for developing silibinin derivatives as anti-tumor agents.","limitations":"synthetic derivatives are not a supplement form; i.v. only, no oral absorption data; n=3 mice; silibinin solubility is a literature value; variance type for Table 4 not stated in table; sampling times not stated"},"37506470":{"pmid":"37506470","title":"Alleviation of acetaminophen-induced liver failure using silibinin nanoliposomes: An in vivo study.","authors":"Gheybi F, Khooei A, Hoseinian A, Doagooyan M, Houshangi K, Jaafari MR, Papi A, Khoddamipour Z, Sahebkar A, Alavizadeh SH","journal":"Biochemical and biophysical research communications","year":"2023","volume":"676","issue":"","pages":"103-108","doi":"10.1016/j.bbrc.2023.07.045","url":"https://pubmed.ncbi.nlm.nih.gov/37506470/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"77","status":"partial","statusNote":"Efficacy study of silibinin nanoliposomes against acetaminophen liver toxicity in mice (i.v. and i.p.). No plasma/tissue silibinin concentrations or PK parameters reported; only liposome entrapment and in vitro release data are absorption-adjacent.","conclusion":"The results of this study support the significant hepatoprotective effect of SLB nanoliposomes against acetaminophen-induced toxicity depending on the route of administration.","limitations":"no PK or tissue concentration data; efficacy study; in vitro release only partially quantified in text (figure)"},"37645028":{"pmid":"37645028","title":"Synthesis, characterization and hepatoprotective effect of silymarin phytosome nanoparticles on ethanol-induced hepatotoxicity in rats.","authors":"Gohari Mahmoudabad A, Gheybi F, Mehrabi M, Masoudi A, Mobasher Z, Vahedi H, Gharravi AM, Bitaraf FS, Rezayat Sorkhabadi SM","journal":"BioImpacts : BI","year":"2023","volume":"13","issue":"4","pages":"301-311","doi":"10.34172/bi.2023.24128","url":"https://pubmed.ncbi.nlm.nih.gov/37645028/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"24","status":"partial","statusNote":"Hepatoprotection study of silymarin phytosome nanoparticles (24 rats, oral gavage 3 weeks). No plasma silymarin or PK parameters; only entrapment, loading and in vitro release data are absorption-adjacent.","conclusion":"Silymarin phytosomal NPs can be used as an efficient treatment for ALD.","limitations":"no PK or plasma silymarin data; efficacy study; release values approximate and mostly in figure; dose equivalence unclear"},"37695023":{"pmid":"37695023","title":"Supplemental impact of silymarin in growing pig diet on the growth performance, total tract digestibility, faecal microflora, faecal noxious gas emission and absorption rate in blood.","authors":"Hossain MM, Hwang HS, Jang SY, Yu S, Kim IH","journal":"Journal of animal physiology and animal nutrition","year":"2024","volume":"108","issue":"1","pages":"206-214","doi":"10.1111/jpn.13879","url":"https://pubmed.ncbi.nlm.nih.gov/37695023/","species":"pig","speciesRaw":"pig","design":"parallel","n":"18 (Experiment 2)","status":"partial","statusNote":"Main Experiment 1 is a growth/digestibility trial (no absorption data). Absorption data only from Experiment 2 (Table 6: plasma silymarin over 24 h, powdered vs micelle-type silymarin in 18 finishing pigs). Growth, ATTD, microbiota, gas outcomes not extracted.","conclusion":"Additionally with the limited number of animal micelle-type silymarin had been found to have a tendency of higher blood absorption rate than powdered silymarin after 1st, 2nd, 4th, 8th, 12th and 24th h of feeding at fattening period.","limitations":"n per treatment NR (18 pigs in 6 groups); no Cmax/AUC/Tmax reported; dose basis unclear (g in diet, per-pig basis NR); single feeding, plasma concentrations very low (ng/mL); authors call results preliminary; micelle-type silymarin composition stated as 20% micelle and 2% silymarin"},"37774895":{"pmid":"37774895","title":"Berberine-silybin salt achieves improved anti-nonalcoholic fatty liver disease effect through regulating lipid metabolism.","authors":"Ma X, Yu X, Li R, Cui J, Yu H, Ren L, Jiang J, Zhang W, Wang L","journal":"Journal of ethnopharmacology","year":"2024","volume":"319","issue":"Pt 2","pages":"117238","doi":"10.1016/j.jep.2023.117238","url":"https://pubmed.ncbi.nlm.nih.gov/37774895/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"partial","statusNote":"Berberine-silybin salt (BSS) vs physical mixture (BSP) paper with NAFLD efficacy focus; PK/permeability/dissolution parts extracted for silybin only (berberine, an off-target compound, not extracted).","conclusion":"The study demonstrated that compared with physical mixing, salification improved the efficacy of BBR and SIY, as demonstrated in animal experiments.","limitations":"n = 5 per group; no significance stats given for AUC differences in Table 3; AUC interval/start not defined; text AUC (10.72) inconsistent with Table 3; SEM variance only; Cmax/Tmax mostly figure-only; combination salt not a supplement form per se; fold-increase basis not stated"},"37964172":{"pmid":"37964172","title":"A comparative study on the preparation and evaluation of solubilizing systems for silymarin.","authors":"Chen Z, Gao W, Feng X, Zhou G, Zhang M, Zeng L, Hu X, Liu Z, Song H","journal":"Drug delivery and translational research","year":"2024","volume":"14","issue":"6","pages":"1616-1634","doi":"10.1007/s13346-023-01476-8","url":"https://pubmed.ncbi.nlm.nih.gov/37964172/","species":"other_animal","speciesRaw":"other animal (beagle dog)","design":"randomized crossover","n":"6","status":"complete","statusNote":"PDF is the Research Square preprint version (posted Sep 2023) of the published Drug Deliv Transl Res article; title matches. Supplementary Table S9 (SC and ISB PK) and supporting information not included in PDF.","conclusion":"Notably, SM-SMEDDS displayed a notably higher in vitro dissolution rate of SM and exhibited a remarkable improvement in the bioavailability of SM compared to SM-SD, SM-PC, SM-SBE-β-CDIC, and even the commercially available product (Legalon®).","limitations":"n = 6 dogs; Table 3 AUC unit printed as ng/L*h; dose basis unclear (30 mg/kg of SM vs product); SC and ISB data only in supplement; preprint version; relative bioavailability from AUC0-t of SB only"},"38093834":{"pmid":"38093834","title":"Liposome-Based Silibinin for Mitigating Nonalcoholic Fatty Liver Disease: Dual Effects via Parenteral and Intestinal Routes.","authors":"Yan B, Zheng X, Wang Y, Yang J, Zhu X, Qiu M, Xia K, Wang Y, Li M, Li S, Ma X, Xie J, Li F, Fu T, Li W","journal":"ACS pharmacology & translational science","year":"2023","volume":"6","issue":"12","pages":"1909-1923","doi":"10.1021/acsptsci.3c00210","url":"https://pubmed.ncbi.nlm.nih.gov/38093834/","species":"rodent","speciesRaw":"rodent","design":"parallel","n":"NR","status":"partial","statusNote":"Efficacy/mechanism study of silibinin liposomes in NAFLD mice and HepG2 cells; absorption data come from a rat oral PK experiment reported only as text (Sil-Lip parameters and fold changes). Free Sil absolute PK values are in Table S1 (supporting information, not in this PDF).","conclusion":"Our study confirmed that Sil-Lip can effectively improve the absorption and bioavailability of Sil, resultantly potentiating its ameliorative effects on NAFLD through modulating intrahepatic insulin resistance-related and NF-κB signaling pathways and extrahepatic gut microbiota.","limitations":"free Sil absolute PK values only in supplement; n = 6 rats; variance type not stated in text; group count inconsistent (three groups, two treatments); time-points/units for AUC (ng/mL·h) interval not stated; no dose basis beyond 50 mg/kg Sil"},"38139990":{"pmid":"38139990","title":"Bovine Serum Albumin Nanoparticles Enhanced the Intranasal Bioavailability of Silybin in Rats.","authors":"Tartari APS, Peczek SH, Fin MT, Ziebarth J, Machado CS, Mainardes RM","journal":"Pharmaceutics","year":"2023","volume":"15","issue":"12","pages":"","doi":"10.3390/pharmaceutics15122648","url":"https://pubmed.ncbi.nlm.nih.gov/38139990/","species":"rodent","speciesRaw":"rodent","design":"parallel (two groups) formulation comparison","n":"14","status":"complete","statusNote":"Silybin (milk thistle) given intranasally to rats as free drug vs BSA nanoparticles; PK table has no variance reported.","conclusion":"the fourfold increase in bioavailability of SLB via intranasal administration of BSA-NP/SLB in a rat model is a significant finding that could revolutionize the administration of SLB and potentially other similar hydrophobic drugs.","limitations":"rat study, intranasal route only; no variance reported in Table 3; small n (7 per group); no oral or IV comparator, so absolute bioavailability not determined; Tmax equal for both arms at earliest sampling time (0.5 h)"},"38144097":{"pmid":"38144097","title":"Designing a Silymarin Nanopercolating System Using CME@ZIF-8: An Approach to Hepatic Injuries.","authors":"Yu H, Saif MS, Hasan M, Zafar A, Zhao X, Waqas M, Tariq T, Xue H, Hussain R","journal":"ACS omega","year":"2023","volume":"8","issue":"50","pages":"48535-48548","doi":"10.1021/acsomega.3c08494","url":"https://pubmed.ncbi.nlm.nih.gov/38144097/","species":"in_vitro","speciesRaw":"in vitro","design":"other (formulation development; in vitro release plus rat CCl4 hepatotoxicity model)","n":"28 rats (in vivo study); in vitro NR","status":"partial","statusNote":"Only in vitro drug-release percentages and drug loading are absorption-related; the rat study measured hepatoprotection (CCl4 model, i.p.) with no plasma PK or absorption measurement, despite claims of improved bioavailability.","conclusion":"Ultimately, our findings highlight the effectiveness of CME@ZIF-8-based silymarin (nanosilymarin) in enhancing the pharmacological effects of the poorly soluble medication silymarin by increasing its solubility and bioavailability.","limitations":"no plasma PK or absorption measured in vivo; bioavailability/solubility claims not supported by presented absorption data; in vitro release only, n and variance NR; release values from text; full curves only in figure; in vivo study is i.p. hepatoprotection, not absorption"},"38353369":{"pmid":"38353369","title":"Unravelling the role of Silibinin in targeting CD44+ cancer stem cells: Therapeutic implications, effective strategies and approaches.","authors":"Lotia S, Patel S, Patel A, Patel V, Shah K, Tanavde V","journal":"Phytotherapy research : PTR","year":"2024","volume":"38","issue":"4","pages":"1830-1837","doi":"10.1002/ptr.8150","url":"https://pubmed.ncbi.nlm.nih.gov/38353369/","species":"in_vitro","speciesRaw":"in vitro","design":"other (narrative review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review (Phytotherapy Research) on silibinin targeting CD44+ cancer stem cells; PubMed publication type Review. Not a primary absorption/PK study.","conclusion":"NR","limitations":"review article, no primary absorption data"},"38529622":{"pmid":"38529622","title":"Rifampin- and Silymarin-Mediated Pharmacokinetic Interactions of Exogenous and Endogenous Substrates in a Transgenic OATP1B Mouse Model.","authors":"Bechtold BJ, Lynch KD, Oyanna VO, Call MR, Graf TN, Oberlies NH, Clarke JD","journal":"Molecular pharmaceutics","year":"2024","volume":"21","issue":"5","pages":"2284-2297","doi":"10.1021/acs.molpharmaceut.3c01088","url":"https://pubmed.ncbi.nlm.nih.gov/38529622/","species":"rodent","speciesRaw":"rodent","design":"parallel groups, drug-interaction PK study","n":"NR","status":"partial","statusNote":"Silymarin flavonolignan PK is on-target (Table 1). Statin/coproporphyrin data are off-target analytes recorded only for vehicle and silymarin groups as interaction context; rifampin-group values not extracted.","conclusion":"we demonstrated the potential utility of the dual humanized OATP1B1/OATP1B3 mice for assessing DDIs and NPDIs.","limitations":"mouse study; silymarin 500 mg/kg dose (authors note about four times allometric human equivalent); silymarin doses/exposures below OATP IC50 values; PRV sampling only to 2 h, fewer than three half-lives; small n and paper inconsistent on n for FVB groups; colony lost, no follow-up experiments; no absolute bioavailability (oral dosing only); CP-I and CP-III showed unexplained vehicle-related decline"},"38794280":{"pmid":"38794280","title":"Evaluation of Silybin Nanoparticles against Liver Damage in Murine Schistosomiasis mansoni Infection.","authors":"Vanzan DF, Goma EP, Locatelli FR, Honorio TDS, Furtado PS, Rodrigues CR, de Sousa VP, Mata Dos Santos HA, do Carmo FA, Simon A, Pyrrho ADS, Ribeiro AJ, Cabral LM","journal":"Pharmaceutics","year":"2024","volume":"16","issue":"5","pages":"","doi":"10.3390/pharmaceutics16050618","url":"https://pubmed.ncbi.nlm.nih.gov/38794280/","species":"in_vitro","speciesRaw":"in vitro","design":"other (formulation development, in vitro permeability/release, in vivo efficacy)","n":"NR","status":"partial","statusNote":"Only in vitro Caco-2 permeability and in vitro release data are absorption-related; the in vivo mouse study measured hepatoprotection markers (ALT/AST etc.) with no plasma PK.","conclusion":"In conclusion, SLN-SIB-U represents a promising nanosystem for enhancing the pharmacokinetic properties of SIB considering the 3Rs approach.","limitations":"no in vivo PK or plasma concentrations measured; bioavailability improvement inferred from ALT effect only; Caco-2 Papp text values only in abstract; units from figure axis; small n (3 per group in vivo); SLN size stability during cell culture/in vivo not shown"},"39079328":{"pmid":"39079328","title":"Effects of micelle silymarin in corn-soybean meal-based diet on laying hens' performance, egg quality, and blood profile, with comparative assessment of blood absorption rates between powdered and micelle silymarin.","authors":"Ahammad GS, Jang SY, Kim IH","journal":"Poultry science","year":"2024","volume":"103","issue":"10","pages":"104029","doi":"10.1016/j.psj.2024.104029","url":"https://pubmed.ncbi.nlm.nih.gov/39079328/","species":"other_animal","speciesRaw":"other animal (laying hens, Hy-Line Brown)","design":"parallel (two dietary groups), Experiment 2; Experiment 1 was a 3-group dose-response feeding trial","n":"192 hens (Experiment 2); 288 hens (Experiment 1)","status":"partial","statusNote":"Only Experiment 2 (blood silymarin 'absorption rate', Table 5) is absorption-related; Experiment 1 covers laying performance, egg quality and liver enzymes. Table 5 prints no units.","conclusion":"In addition, the incorporation of MS demonstrated higher blood absorption rates compared to powder-type silymarin.","limitations":"no units for the absorption values; only 0, 2 and 4 h sampling, no Cmax/AUC; n sampled not stated; timing of sampling relative to feeding not stated; dose basis unclear (4% of diet; micelle product has minimum 2% silymarin); authors call findings preliminary"},"39204378":{"pmid":"39204378","title":"Nanocrystal Formulation to Enhance Oral Absorption of Silybin: Preparation, In Vitro Evaluations, and Pharmacokinetic Evaluations in Rats and Healthy Human Subjects.","authors":"Seo S, Kim GY, Kim MH, Lee KW, Kim MJ, Chaudhary M, Bikram K, Kim T, Choi S, Yang H, Park JW, Kim DD, Kim KT","journal":"Pharmaceutics","year":"2024","volume":"16","issue":"8","pages":"","doi":"10.3390/pharmaceutics16081033","url":"https://pubmed.ncbi.nlm.nih.gov/39204378/","species":"human","speciesRaw":"human","design":"randomized crossover (human; two-period, single-dose); parallel groups in rats","n":"14 humans; rats NR in Methods (n = 5 per Fig. 8 legend)","status":"complete","statusNote":"","conclusion":"In addition, the oral bioavailability of silybin from HM40 in rats and humans was enhanced by 2.61- and 1.51-fold, respectively, compared to that from the milk thistle raw material.","limitations":"Methods give no rat n (5 per Fig. 8 legend); no variance for rat Tmax; human study had 13 males and 1 female; AUCinf units/time not stated for sampling truncation in rats (sampling to 6 h); industry-affiliated authors; Tmax at first or earliest sampling in rats limits resolution"},"39221555":{"pmid":"39221555","title":"Evaluation of efficacy of cholecalciferol and silymarin in improving lower urinary tract symptoms of benign prostatic hyperplasia: A double-blind, randomized, controlled trial.","authors":"Valipour R, Narouie B, Momeni H, Radpour N, Torabinavid P, Momeni A, Jowzi A","journal":"Urologia","year":"2024","volume":"91","issue":"4","pages":"727-737","doi":"10.1177/03915603241274467","url":"https://pubmed.ncbi.nlm.nih.gov/39221555/","species":"human","speciesRaw":"human","design":"RCT","n":"80 enrolled; 68 completed","status":"not absorption-related","statusNote":"Efficacy RCT of silymarin 240 mg every 12 h and/or cholecalciferol 50,000 IU/wk on BPH lower urinary tract symptoms (IPSS, Qmax, prostate volume, PVR, PSA). No silymarin absorption or PK data; serum 25-(OH) vitamin D is only reported as a cholecalciferol/stratification variable.","conclusion":"NR","limitations":"efficacy trial, no absorption data"},"39310970":{"pmid":"39310970","title":"Silybin: A Review of Its Targeted and Novel Agents for Treating Liver Diseases Based on Pathogenesis.","authors":"Wu J, Wen L, Liu X, Li Q, Sun Z, Liang C, Xie F, Li X","journal":"Phytotherapy research : PTR","year":"2024","volume":"38","issue":"12","pages":"5713-5740","doi":"10.1002/ptr.8347","url":"https://pubmed.ncbi.nlm.nih.gov/39310970/","species":"in_vitro","speciesRaw":"in vitro","design":"other (narrative review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review (Phytotherapy Research) of silybin formulations and targeted delivery for liver diseases; PubMed publication type Review. Not a primary absorption/PK study.","conclusion":"NR","limitations":"review article, no primary absorption data"},"39344123":{"pmid":"39344123","title":"Potential of CME@ZIF-8 MOF Nanoformulation: Smart Delivery of Silymarin for Enhanced Performance and Mechanism in Albino Rats.","authors":"Saif MS, Waqas M, Hussain R, Ahmed MM, Tariq T, Batool S, Liu Q, Mustafa G, Hasan M","journal":"ACS applied bio materials","year":"2024","volume":"7","issue":"10","pages":"6919-6931","doi":"10.1021/acsabm.4c01019","url":"https://pubmed.ncbi.nlm.nih.gov/39344123/","species":"in_vitro","speciesRaw":"in vitro; albino rats","design":"in vitro release study; parallel-group rat efficacy study","n":"NR","status":"partial","statusNote":"Only in vitro release and drug loading are absorption-related; the in vivo CCl4 nephro/cardioprotection study reports no pharmacokinetic data.","conclusion":"This study showed how important CME@ZIF-8 MOFs are for boosting silymarin's absorption, solubility, and in vivo nephron-cardioprotective benefits.","limitations":"No in vivo pharmacokinetic data despite absorption/bioavailability claims; n and variance not reported for release data; analytical method NR in extracted data"},"39370820":{"pmid":"39370820","title":"The Pharmacokinetics and Liver-Targeting Evaluation of Silybin Liposomes Mediated by the NTCP/OCTN2 Dual Receptors.","authors":"Cui J, Wen Z, Huang H, Qin S, Luo Y, Zhang W, Wu W","journal":"Molecular pharmaceutics","year":"2024","volume":"21","issue":"10","pages":"4912-4923","doi":"10.1021/acs.molpharmaceut.3c01245","url":"https://pubmed.ncbi.nlm.nih.gov/39370820/","species":"rodent","speciesRaw":"rodent","design":"other (preclinical formulation, IV biodistribution; parallel groups)","n":"NR","status":"partial","statusNote":"Mouse IV tissue-distribution study of silybin liposomes (animal, IV route = on-target). Nearly all tissue concentration-time data are figure-only; the only AUC in text is liver AUC for MyrB/LC-Lip@SB. No oral absorption data.","conclusion":"In summary, the developed delivery system increases liver uptake levels and decreases accumulation in off-target tissues by mimicking HBV-targeting properties.","limitations":"intravenous route only, no oral absorption; tissue data figure-only; no p-values for in vivo comparisons in text; units of Table 2 PBPK parameters not stated; no dose in mass units stated (concentration and volume only)"},"39418531":{"pmid":"39418531","title":"Novel Silybin-Conjugated Chitosan Polymeric Micelles for Improving the Oral Absorption of Doxorubicin Based on the Inhibition of P-gp and CYP3A4.","authors":"Yang Y, Chen Y, Wei Y, Wu W, Wang Q, Xue T, Zhang X, Chen W, Zhang W","journal":"Biomacromolecules","year":"2024","volume":"25","issue":"11","pages":"7146-7155","doi":"10.1021/acs.biomac.4c00628","url":"https://pubmed.ncbi.nlm.nih.gov/39418531/","species":"rodent","speciesRaw":"rodent","design":"parallel (3 groups), preclinical","n":"15","status":"off-target analyte","statusNote":"Rat oral PK of doxorubicin (DOX); silybin is the carrier material (CS-SB micelles) or co-administered, and silybin plasma levels were not measured. DOX PK values recorded for reference.","conclusion":"The novel micelle system possessed the capacity to enhance the intestinal absorption of DOX and the potential to reduce DOX cardiotoxicity.","limitations":"off-target analyte (doxorubicin, not silybin); no variance printed in Table 1; small n; silybin dose not stated for mixture arm"},"39444787":{"pmid":"39444787","title":"Novel Strategies Enhancing Bioavailability and Therapeutical Potential of Silibinin for Treatment of Liver Disorders.","authors":"Selc M, Macova R, Babelova A","journal":"Drug design, development and therapy","year":"2024","volume":"18","issue":"","pages":"4629-4659","doi":"10.2147/DDDT.S483140","url":"https://pubmed.ncbi.nlm.nih.gov/39444787/","species":"other_animal","speciesRaw":"other animal (review)","design":"other (narrative review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review (Drug Des Devel Ther 2024) of silibinin bioavailability strategies and liver disease; no primary PK data. Data sections skipped.","conclusion":"NR","limitations":"review, not primary data"},"39498271":{"pmid":"39498271","title":"Study on the preparation of stabilizer-free silymarin nanocrystals and its oral absorption mechanisms.","authors":"Tu L, Han P, Sun Y, Jin Y, Hu K, Cheng M, Shao Y, Feng J, Yuan F","journal":"International journal of pharmaceutics: X","year":"2024","volume":"8","issue":"","pages":"100292","doi":"10.1016/j.ijpx.2024.100292","url":"https://pubmed.ncbi.nlm.nih.gov/39498271/","species":"rodent","speciesRaw":"rodent","design":"parallel (3 groups), preclinical formulation comparison","n":"15","status":"complete","statusNote":"","conclusion":"The results of pharmacokinetic parameters indicated that SM-NC improved oral bioavailability in rats compared to Crude-SM.","limitations":"small n (5 per group); units for AUC printed as µg·L−1; CLz/F unit not printed; figure-only concentration-time curves; dose basis NR"},"39567122":{"pmid":"39567122","title":"Microwave-assisted, sulfhydryl-modified β-cyclodextrin-silymarin inclusion complex: A diverse approach to improve oral drug bioavailability via enhanced mucoadhesion and permeation.","authors":"Arshad S, Raza SA, Alamgeer, Bukhari SNA, Alotaibi NF, Ahmad N, Irfan HM, Mahmood A, Asim MH","journal":"Carbohydrate polymers","year":"2025","volume":"348","issue":"Pt B","pages":"122880","doi":"10.1016/j.carbpol.2024.122880","url":"https://pubmed.ncbi.nlm.nih.gov/39567122/","species":"rodent","speciesRaw":"rodent","design":"parallel (4 groups), preclinical formulation comparison","n":"NR","status":"complete","statusNote":"","conclusion":"Moreover, in-vivo studies confirmed a significantly improved oral bioavailability of SMN due to incorporation in sulfhydryl-modified β-CD.","limitations":"n inconsistent (6 vs 3); IV dose inconsistent (70 vs 50 mg/kg); sampling times not stated in text; Fr labelled relative but computed vs IV; dose basis NR"},"39596784":{"pmid":"39596784","title":"A Comprehensive Review on the Antibacterial, Antifungal, Antiviral, and Antiparasitic Potential of Silybin.","authors":"Pereira-Filho JL, Mendes AGG, Campos CDL, Moreira IV, Monteiro CRAV, Soczek SHDS, Fernandes ES, Carvalho RC, Monteiro-Neto V","journal":"Antibiotics (Basel, Switzerland)","year":"2024","volume":"13","issue":"11","pages":"","doi":"10.3390/antibiotics13111091","url":"https://pubmed.ncbi.nlm.nih.gov/39596784/","species":"other_animal","speciesRaw":"other animal (review)","design":"other (narrative review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review (Antibiotics 2024) of silybin antibacterial, antifungal, antiviral and antiparasitic activity; not an absorption/PK primary study. Data sections skipped.","conclusion":"NR","limitations":"review, not primary data; antimicrobial focus, not absorption"},"39861153":{"pmid":"39861153","title":"Silybin Cocrystals with Improved Solubility and Bioavailability.","authors":"Zhu B, Ding Z, Rong X, Li S, Mei X","journal":"Pharmaceuticals (Basel, Switzerland)","year":"2025","volume":"18","issue":"1","pages":"","doi":"10.3390/ph18010090","url":"https://pubmed.ncbi.nlm.nih.gov/39861153/","species":"rodent","speciesRaw":"rodent","design":"parallel (3 groups), randomized, preclinical formulation comparison","n":"18","status":"complete","statusNote":"","conclusion":"At the same dosage, the Silybin cocrystal achieved a 16.4-fold increase in Cmax and a 16.2-fold improvement in AUC0–8h compared to raw Silybin, and also significantly surpassed the bioavailability of the commercial Silybin–phosphatidylcholine complex.","limitations":"small n (6 per group); no statistical test reported for PK differences; Tmax first sample (0.17 h) for all arms, early peak; oil vehicle; single dose level; large SD"},"40006559":{"pmid":"40006559","title":"Development and Characterization of Silibinin-Loaded Nanoemulsions: A Promising Mucoadhesive Platform for Enhanced Mucosal Drug Delivery.","authors":"Tartari APS, Jacumazo J, Lorenzett AKP, Freitas RA, Mainardes RM","journal":"Pharmaceutics","year":"2025","volume":"17","issue":"2","pages":"","doi":"10.3390/pharmaceutics17020192","url":"https://pubmed.ncbi.nlm.nih.gov/40006559/","species":"in_vitro","speciesRaw":"in vitro","design":"other (formulation characterisation)","n":"NR","status":"not absorption-related","statusNote":"Formulation development and physicochemical characterisation of silibinin nanoemulsions (solubility in excipients, phase diagrams, particle size, rheology, QCM-D mucoadhesion, surface tension). No PK, permeation, release or absorption measurements. Data sections skipped.","conclusion":"These findings underscore the suitability of SLB-loaded nanoemulsions as a robust platform for effective mucosal drug delivery, addressing solubility and bioavailability challenges while enabling prolonged retention and controlled therapeutic release.","limitations":"no absorption or PK data; solubility in excipients only"},"40158557":{"pmid":"40158557","title":"Anticancer effects of silymarin-loaded ACA-HA/sulfonamide IR-MOF nanoplatform in CT-26 xenograft model.","authors":"Alavinia S, Ghorbani-Vaghei R, Haddadi R, Sanemar K, Uroomiye SS, Nourian A, Emami N","journal":"International journal of biological macromolecules","year":"2025","volume":"309","issue":"Pt 1","pages":"142651","doi":"10.1016/j.ijbiomac.2025.142651","url":"https://pubmed.ncbi.nlm.nih.gov/40158557/","species":"in_vitro","speciesRaw":"in vitro","design":"other (formulation and anticancer efficacy study)","n":"NR","status":"not absorption-related","statusNote":"Anticancer efficacy study of silymarin loaded in a Sul-IRMOF-ACA-HA metal-organic framework (CT-26 cells, intratumoral injection in BALB/c mice, oxidative stress markers). Only in vitro cumulative release (UV, dialysis) and loading efficiency are reported; no plasma/tissue PK or permeation data. Data sections skipped.","conclusion":"NR","limitations":"no absorption or PK data"},"40493802":{"pmid":"40493802","title":"Discovery of a Novel Silybin Derivative for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis.","authors":"Sui Z, Li M, Wang X, Luo C, Chen L, Deng X, Li M, Liu L, Huang X, Zhu X, Nie C, Ni S, Ye J, Peng S, Peng B, Ma Z, Luo Z, Liu S, Ma D","journal":"Journal of medicinal chemistry","year":"2025","volume":"68","issue":"12","pages":"12786-12799","doi":"10.1021/acs.jmedchem.5c00672","url":"https://pubmed.ncbi.nlm.nih.gov/40493802/","species":"rodent","speciesRaw":"rodent","design":"parallel, preclinical","n":"10","status":"partial","statusNote":"Primary PK data are for silybin and for its semisynthetic derivative A2 after a single oral dose in rats (Table 3). A2 rows are a derivative, not silybin. Most of the paper is efficacy (MASH models) and is not extracted. Concentration-time curves are in the SI.","conclusion":"Furthermore, A2 showed much better bioavailability than silybin and also had a low toxicity profile.","limitations":"small n (5 per group); 10 rats total in Methods; no oral bioavailability vs IV reported; PK method details in SI; curves not in main text; A2 is a derivative"},"40685047":{"pmid":"40685047","title":"Chitosan-decorated silibinin-hyaluronic acid conjugate for enhancing intestinal absorption and improving liver fibrosis.","authors":"Wang C, Cui JJ, Sheng T, Xia S, Li JM, Zhang BF","journal":"International journal of biological macromolecules","year":"2025","volume":"320","issue":"Pt 4","pages":"146057","doi":"10.1016/j.ijbiomac.2025.146057","url":"https://pubmed.ncbi.nlm.nih.gov/40685047/","species":"rodent","speciesRaw":"rodent","design":"other (parallel-group animal PK, in situ intestinal loop, in vitro release)","n":"NR","status":"complete","statusNote":"Rat PK of silibinin (SLB) as free SLB vs HA-SLB prodrug nanoparticles vs chitosan-coated CS/HA-SLB NPs; also in vitro release, rat intestinal loop uptake, tissue distribution (figure only) and mouse efficacy (not extracted).","conclusion":"Compared with the free SLB group, the CS/HA-SLB NPs group can increase the T1/2 and AUC of SLB, thereby prolonging the circulation time in the body and improving the oral bioavailability of SLB.","limitations":"rat study with small n (6 PK, 4 intestinal loop/tissue); no absolute or relative bioavailability value reported (AUC0→∞ only; no IV arm); dose formulation of free SLB comparator and fasting state of PK rats not stated; several data figure-only (plasma curves, intestinal loop, tissue distribution, pH 6.8 release for free SLB and HA-SLB); sex-mixed rats pooled; no per-sex data"},"40733088":{"pmid":"40733088","title":"Novel Micellar Formulation of Silymarin (Milk Thistle) with Enhanced Bioavailability in a Double-Blind, Randomized, Crossover Human Trial.","authors":"Chang C, Zhang Y, Kuo YC, Du M, Roh K, Gahler R, Ibi A, Solnier J","journal":"Pharmaceutics","year":"2025","volume":"17","issue":"7","pages":"","doi":"10.3390/pharmaceutics17070880","url":"https://pubmed.ncbi.nlm.nih.gov/40733088/","species":"human","speciesRaw":"human","design":"randomized crossover (double-blind)","n":"16","status":"complete","statusNote":"Randomized crossover PK of micellar (LipoMicel, LMM) vs standard silymarin capsule; PK table values extracted; several abstract/text vs Table 3 inconsistencies recorded.","conclusion":"the LipoMicel milk thistle formulation (LMM) exhibited significantly faster absorption, higher peak plasma concentrations, and greater overall exposure (AUC0–24) compared to the unformulated product, but it has a shorter mean residence time.","limitations":"small n (16); no excipient-only control; formulation effect not separable from MCT/phosphatidylcholine; blinding possibly compromised (hard-gel vs soft-gel capsules); capillary whole blood, total silymarin only; individual flavonolignans not reported; STD and LMM have different silymarin component composition; several p-values and STD Tmax inconsistent between abstract/text and Table 3; single dose only; fed state only; funder/manufacturer-related authors"},"40992023":{"pmid":"40992023","title":"A hepatocyte targeted silymarin sea cucumber peptide-galactose nanoparticle for the alleviation of ethanol-induced damage in cells.","authors":"Hao S, Wang Y, Lv Y, Liu K, Tan M","journal":"Colloids and surfaces. B, Biointerfaces","year":"2026","volume":"257","issue":"","pages":"115152","doi":"10.1016/j.colsurfb.2025.115152","url":"https://pubmed.ncbi.nlm.nih.gov/40992023/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro formulation and cell study)","n":"NR","status":"partial","statusNote":"In vitro formulation/cell study of silymarin-loaded sea cucumber peptide-galactose nanoparticles (silymarin@SCP-Gal) in LO2 cells; no animal or human PK. Only in vitro release %, encapsulation efficiency and loading are numeric; cellular uptake is qualitative/figure-only and measured with FITC-labelled carrier, not silymarin.","conclusion":"Collectively, these findings highlight the promise of Gal-glycosylated SCP-based nanoparticles as an effective system for targeted delivery of silymarin, providing substantial protection against ethanol-induced cellular injury.","limitations":"in vitro only; authors state study limited to in vitro validation; no pharmacokinetic or absorption (Caco-2 or in vivo) data; cellular uptake measured with FITC-labelled carrier, figure-only; no free silymarin release comparator reported in text"},"41156530":{"pmid":"41156530","title":"Hepatoprotective Effect of Silymarin Herb in Prevention of Liver Dysfunction Using Pig as Animal Model.","authors":"Sharma P, Asediya V, Kalra G, Sultana S, Purohit N, Kibitlewska K, Kozera W, Czarnik U, Karpiesiuk K, Lecewicz M, Wysocki P, Lepczyński A, Ożgo M, Marynowska M, Herosimczyk A, Redlarska E, Ślaska B, Kowal K, Tkaczyk-Wlizło A, Grychnik P, Kurian AP, Ziółkowska-Twarowska K, Chałaśkiewicz K, Kępka-Borkowska K, Poławska E, Ogłuszka M, Starzyński RR, Taniguchi H, Pareek CS, Pierzchała M","journal":"Nutrients","year":"2025","volume":"17","issue":"20","pages":"","doi":"10.3390/nu17203278","url":"https://pubmed.ncbi.nlm.nih.gov/41156530/","species":"unclear","speciesRaw":"NR","design":"NR","n":"NR","status":"review/non-primary","statusNote":"Narrative review (Nutrients 2025, 17, 3278) of silymarin chemistry, pharmacokinetics and hepatoprotection in porcine models; not a primary PK study. Data sections skipped per rules.","conclusion":"NR","limitations":""},"41196338":{"pmid":"41196338","title":"Targeting metabolic dysfunction-associated steatotic liver disease with phytosomal silymarin and piperine: A natural alternative to fenofibrate in a rat model.","authors":"Tawfik MF, Hussein YS, Hasanin AH, Baher W, El-Khazragy N, Moawad FG, El-Khair MA, El-Sayed SM","journal":"Naunyn-Schmiedeberg's archives of pharmacology","year":"2026","volume":"399","issue":"4","pages":"5559-5574","doi":"10.1007/s00210-025-04752-1","url":"https://pubmed.ncbi.nlm.nih.gov/41196338/","species":"unclear","speciesRaw":"NR","design":"NR","n":"NR","status":"not absorption-related","statusNote":"Efficacy study in oxytetracycline-induced MASLD rats (silymarin vs silymarin-piperine-lecithin phytocomplex vs fenofibrate, 90 days; ALT/AST/lipids/histology/PPAR-alpha). No plasma/tissue silymarin concentrations or PK parameters measured; authors list absence of pharmacokinetic and bioavailability assessments as a limitation.","conclusion":"NR","limitations":""},"41394134":{"pmid":"41394134","title":"Silymarin as a phytopharmaceutical agent: advances in mechanistic insights, formulation strategies, and pre-clinical applications.","authors":"Sayyad M, Sutar AD, Shivhare K, Shukla R, Flora SJS","journal":"Frontiers in pharmacology","year":"2025","volume":"16","issue":"","pages":"1711653","doi":"10.3389/fphar.2025.1711653","url":"https://pubmed.ncbi.nlm.nih.gov/41394134/","species":"unclear","speciesRaw":"NR","design":"NR","n":"NR","status":"review/non-primary","statusNote":"Review article (Front. Pharmacol. 2025, 16:1711653) on silymarin mechanisms, pharmacokinetics, formulation strategies and pre-clinical applications; not a primary study. Data sections skipped per rules.","conclusion":"NR","limitations":""},"41406786":{"pmid":"41406786","title":"Design and synthesis of new Silybin-carnosine conjugates with antioxidant and cytoprotective effects in LPS-treated RAW264.7 macrophages.","authors":"Romanucci V, Naletova I, Pagano R, Petrone M, Attanasio F, Zarrelli A, Milardi D, Di Fabio G","journal":"Bioorganic chemistry","year":"2026","volume":"168","issue":"","pages":"109351","doi":"10.1016/j.bioorg.2025.109351","url":"https://pubmed.ncbi.nlm.nih.gov/41406786/","species":"unclear","speciesRaw":"NR","design":"NR","n":"NR","status":"not absorption-related","statusNote":"Medicinal chemistry/in vitro paper: synthesis of silybin-carnosine phosphodiester conjugates (SilpCar) and antioxidant (DPPH, ORAC) and cytoprotective effects in LPS-treated RAW264.7 macrophages. No absorption or PK data; only qualitative serum stability of the conjugates (unchanged over 24 h, data in Supporting Information S43, not in the PDF).","conclusion":"NR","limitations":""},"41471139":{"pmid":"41471139","title":"Silymarin and Silybin: Rejuvenating Traditional Remedies with Modern Delivery Strategies.","authors":"Li X, Zhu H, Wang Y, Zhang X, Yang Z, Yan X, Yu Q","journal":"Pharmaceutics","year":"2025","volume":"17","issue":"12","pages":"","doi":"10.3390/pharmaceutics17121628","url":"https://pubmed.ncbi.nlm.nih.gov/41471139/","species":"unclear","speciesRaw":"NR","design":"NR","n":"NR","status":"review/non-primary","statusNote":"Review article (Pharmaceutics 2025, 17, 1628) of silymarin/silybin pharmacokinetic barriers and delivery strategies; not a primary study. Data sections skipped per rules.","conclusion":"NR","limitations":""},"41722252":{"pmid":"41722252","title":"Silibinin-loaded PEGylated niosomal nanoparticles restore hippocampus histological changes, memory and learning, and downregulate the inflammasome pathway in Alzheimer's disease animal models.","authors":"Kiani K, Ramezani M, Jafari-Gharabaghlou D, Amiri I, Soleimani Asl S, Mirzaei F","journal":"Biochemical and biophysical research communications","year":"2026","volume":"809","issue":"","pages":"153496","doi":"10.1016/j.bbrc.2026.153496","url":"https://pubmed.ncbi.nlm.nih.gov/41722252/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro release plus animal efficacy study)","n":"40 rats (efficacy study)","status":"partial","statusNote":"Efficacy study (Abeta1-42 rat Alzheimer model; memory tests, inflammasome gene expression, histology) of silibinin-loaded PEGylated niosomes vs free silibinin. No plasma/tissue silibinin concentrations or PK measured. Only numeric absorption-adjacent data are in vitro cumulative release percentages.","conclusion":"These findings suggest that PEGylated Silibinin-loaded niosomal nanoparticles are an effective option for improving Alzheimer's disease complications by modulating the inflammasome pathway and amyloid plaque aggregation.","limitations":"no pharmacokinetic or tissue concentration data; in vitro release only, no free silibinin release comparator reported; rat efficacy outcomes only"},"41729747":{"pmid":"41729747","title":"In vitro and ex vivo Cutaneous Bioavailability and Biotransformation of Silymarin and Its Constituents.","authors":"Vostálová J, Kosina P, Zálešák B, Valentová K, Papoušková B, Ryšavá A, Hanyk J, Rajnochová Svobodová A","journal":"Skin pharmacology and physiology","year":"2026","volume":"","issue":"","pages":"1-20","doi":"10.1159/000550859","url":"https://pubmed.ncbi.nlm.nih.gov/41729747/","species":"in_vitro","speciesRaw":"in vitro","design":"other (in vitro and ex vivo uptake and biotransformation study)","n":"NR","status":"complete","statusNote":"In vitro (human dermal fibroblasts) and ex vivo (human skin explant) uptake and biotransformation of silymarin and its pure constituents; UHPLC-MS peak areas, semiquantitative only; no PK parameters, no topical or oral dosing. Tables 1-8 extracted as printed (all columns), table cell colour (semiquantitative concentration levels) not recorded.","conclusion":"Here, we found that polyphenol constituents of SM penetrate into human skin cells and tissue depending on their lipophilicity [28]. In skin fibroblasts and tissue, they are converted into various metabolites.","limitations":"in vitro/ex vivo only; no PK parameters; semiquantitative peak areas, calibration in solvent not matrix, no unit printed; substances submerged in medium rather than applied topically to stratum corneum (authors note penetration through tissue edges); n = 3, no statistical tests reported for table values; some test compounds impure or unstable (DHSB, SD, TA)"},"42054809":{"pmid":"42054809","title":"Silibinin as a modulator of redox-onco axis: A natural inhibitor of oxidative damage and tumor progression.","authors":"Tanoy NM, Chowdhury MN, Tasnim Z, Riya MRR, Momin MA, Sadekuzzaman M, Mow SI, Sabuj MSS, Talha MMH, Akanda MR","journal":"Pathology, research and practice","year":"2026","volume":"283","issue":"","pages":"156495","doi":"10.1016/j.prp.2026.156495","url":"https://pubmed.ncbi.nlm.nih.gov/42054809/","species":"other_animal","speciesRaw":"other animal (review)","design":"other (narrative review)","n":"NR","status":"review/non-primary","statusNote":"Narrative review of silibinin and the redox-onco axis (Pathology - Research and Practice 283, 156495); not a primary absorption/PK study.","conclusion":"()","limitations":"review, no primary data extracted"},"42190474":{"pmid":"42190474","title":"Hepatoprotective efficacy of silymarin-loaded metal-organic frameworks against CCl(4) toxicity in broilers: A dose-dependent study.","authors":"Aldawood N, Arshad M, Hussain R, Hasan M, Al-Rasheed M, Mohamed MHA, Meligy AMA, Ahmed MS, Alfifi A, Ahmed AE","journal":"Poultry science","year":"2026","volume":"105","issue":"8","pages":"107082","doi":"10.1016/j.psj.2026.107082","url":"https://pubmed.ncbi.nlm.nih.gov/42190474/","species":"other_animal","speciesRaw":"other animal (broiler chicken)","design":"other (randomized efficacy study, 7 groups)","n":"105","status":"not absorption-related","statusNote":"Hepatoprotective efficacy study of silymarin@ZIF-8 vs conventional silymarin in CCl4-intoxicated broilers; outcomes are body/liver weight, hematology, liver enzymes, oxidative markers, histopathology, comet assay. No silymarin concentration/PK/absorption measured; bioavailability is only inferred by the authors from efficacy.","conclusion":"()","limitations":"no absorption/PK data; bioavailability only inferred from efficacy"},"42235156":{"pmid":"42235156","title":"Insights into the therapeutic potential of silymarin-encapsulated CME@ZIF-8 against CCl(4)-induced toxicity in broiler chicks.","authors":"Jiabin Z, Al-Rasheed M, Rauf A, Hussain R, Mohammed ESI, Momenah MA, Mohamed MHA, Meligy AMA, Ahmed MS, Alfifi A, Ahmed AE, Shiqi D","journal":"Poultry science","year":"2026","volume":"105","issue":"9","pages":"107176","doi":"10.1016/j.psj.2026.107176","url":"https://pubmed.ncbi.nlm.nih.gov/42235156/","species":"other_animal","speciesRaw":"other animal (broiler chick)","design":"other (randomized efficacy study)","n":"NR","status":"not absorption-related","statusNote":"Protective-efficacy study of Sil@CME@ZIF-8 vs silymarin against CCl4-induced toxicity in brain, spleen and intestine of broiler chicks (organ weights, oxidative markers, histopathology, comet assay). No silymarin concentration/PK/absorption measured; authors state PK and bioavailability data are lacking.","conclusion":"()","limitations":"no absorption/PK data"},"42264004":{"pmid":"42264004","title":"Study on the improvement of bioavailability and hepatoprotective effect of silybin-7-eicosanedioate long-acting injection based on prodrug technology.","authors":"Zhou J, Wei R, Li B, Guo B, Chen X, Kuang Y, Xu Y, Wu X","journal":"European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V","year":"2026","volume":"226","issue":"","pages":"115144","doi":"10.1016/j.ejpb.2026.115144","url":"https://pubmed.ncbi.nlm.nih.gov/42264004/","species":"rodent","speciesRaw":"rodent","design":"parallel (2 groups) PK study of an injectable prodrug vs oral capsule","n":"12","status":"complete","statusNote":"Rat PK of intramuscular silybin-7-eicosanedioate (SLB-7-ODDA) long-acting suspension vs oral silybin capsule; in vitro release/conversion are figure-only. Rest of paper is synthesis, stability, pharmacodynamics, irritation.","conclusion":"In conclusion, this formulation significantly prolonged the half-life of SLB, reduced the dosing frequency, and demonstrated excellent sustained-release characteristics and in vivo retention capacity.","limitations":"Units for AUC and Cmax printed as g/L·h and g/L in Table 11, text says μg/mL; Comparator product named inconsistently; IM vs oral comparison with different doses (135 vs 18.90 mg/kg); Basis of relative bioavailability calculation not stated; Rat study only, small n; Self-prepared prodrug; industry-affiliated authors"},"42497478":{"pmid":"42497478","title":"Silica-installed redox nanoparticles enable effective oral silymarin therapy for liver fibrosis.","authors":"Thi Nguyen TH, Thi Tran H, Lam AT, Trinh NT, Tran HH, Nagasaki Y, Vong LB","journal":"Colloids and surfaces. B, Biointerfaces","year":"2026","volume":"268","issue":"Pt 1","pages":"116000","doi":"10.1016/j.colsurfb.2026.116000","url":"https://pubmed.ncbi.nlm.nih.gov/42497478/","species":"rodent","speciesRaw":"rodent","design":"other (formulation comparison, free vs nanoparticle)","n":"NR","status":"partial","statusNote":"Formulation paper; absorption-relevant data limited to hepatic silymarin accumulation 0.5 and 1 h after oral dosing in mice (Fig. 2F, figure only), in vitro cell uptake and release (figures only). Text gives no numeric hepatic concentrations or plasma PK; plasma PK cited from earlier papers.","conclusion":"These results demonstrate that siRNP is an effective oral nanoplatform for enhancing the therapeutic efficacy of hydrophobic drugs and highlight the potential of Sil@siRNP as a promising strategy for the treatment of liver fibrosis.","limitations":"hepatic concentrations figure-only; no plasma PK in this paper; dose in accumulation experiment not stated; only 2 early time points; n=3; bioavailability inferred, not measured"},"42660255":{"pmid":"42660255","title":"Co-delivery of doxorubicin and silybin via taurine-conjugated chitosan-modified TAUT-targeted liposomes enhances oral bioavailability and alleviates doxorubicin-induced cardiomyocyte toxicity in vitro.","authors":"Qin S, Zhang W, Luo Y, Tang X, Wu W","journal":"International journal of biological macromolecules","year":"2026","volume":"382","issue":"Pt 1","pages":"154244","doi":"10.1016/j.ijbiomac.2026.154244","url":"https://pubmed.ncbi.nlm.nih.gov/42660255/","species":"in_vitro","speciesRaw":"in vitro","design":"other (formulation study)","n":"NR","status":"partial","statusNote":"Co-delivery liposome study aimed at oral doxorubicin (DOX) bioavailability; silybin (SLB) is a co-loaded P-gp/CYP3A4 inhibitor. Oral PK in rats (absolute bioavailability 28.89%, Cmax 0.377 ug/mL, t1/2 34.8 h) is of DOX, an off-target analyte, so not extracted. SLB itself was measured only in in vitro release (extracted); SLB plasma PK not reported.","conclusion":"Collectively, these findings establish taurine transporter (TAUT)-targeted DOX/SLB co-loaded liposomes as an oral delivery platform that enhances DOX systemic exposure through intestinal uptake and metabolic-barrier modulation while reducing DOX-induced cardiomyocyte toxicity in vitro.","limitations":"silybin used as absorption enhancer; no SLB plasma PK; DOX is the PK analyte; full PK table in supplement not available; SLB release values from text only"},"42785882":{"pmid":"42785882","title":"Novel pyrimidine nucleoside - chitosan - silybin micelles for improving the oral absorption of doxorubicin via intestinal nucleoside transporter.","authors":"Chen Y, Wei Y, Li Q, He H, Chen H, Zhang H, Rong X, Liang X, Lin S, Zhang W","journal":"Carbohydrate polymers","year":"2026","volume":"391","issue":"","pages":"125843","doi":"10.1016/j.carbpol.2026.125843","url":"https://pubmed.ncbi.nlm.nih.gov/42785882/","species":"rodent","speciesRaw":"rodent","design":"parallel (formulation comparison)","n":"NR","status":"off-target analyte","statusNote":"Oral absorption/PK study of doxorubicin (DOX) delivered in pyrimidine nucleoside-chitosan-silybin (PYN-CS-SB) micelles; silybin is a polymer-conjugated P-gp/CYP3A4 inhibitor and its own concentration, release or absorption was not measured. PK analyte is DOX (e.g. 391% relative oral bioavailability of DCD-CS-SB@DOX vs DOX.HCl).","conclusion":"The findings showed the extensive potential of intestinal nucleoside transporter mediated PYN-CS-SB micelles in oral drug delivery.","limitations":"silybin not measured; DOX is the PK analyte"},"42892542":{"pmid":"42892542","title":"Metabolism-mediated herb-drug interaction between milk thistle and resmetirom in MCD diet-induced metabolic dysfunction-associated steatohepatitis rat model.","authors":"Gajula SNR, Savana S, Saripilli VY, Nalla LV","journal":"Biochemical pharmacology","year":"2026","volume":"254","issue":"Pt 3","pages":"118548","doi":"10.1016/j.bcp.2026.118548","url":"https://pubmed.ncbi.nlm.nih.gov/42892542/","species":"rodent","speciesRaw":"rodent","design":"parallel (4 groups: vehicle, resmetirom 8 mg/kg, milk thistle, combination), 8 days","n":"NR","status":"off-target analyte","statusNote":"Herb-drug interaction PK study: resmetirom plasma PK and microsomal stability in MCD-diet MASH rats with/without milk thistle supplement. Only resmetirom was quantified in plasma; silybin A+B was quantified only as supplement content (HPLC standardization), not absorbed silybin.","conclusion":"These findings provide preclinical evidence of a metabolism-mediated milk thistle-resmetirom interaction that increases resmetirom exposure and is accompanied by an enhanced pharmacodynamic response in rats.","limitations":"silybin absorption not measured; rat disease model"},"42956604":{"pmid":"42956604","title":"Microencapsulated silymarin nanoparticles prepared by atomized instantaneous solidification: Structural characterization, molecular interactions, improved solubility and bioavailability.","authors":"Zhang F, Yan W, Xu M, Yu J, Xie Y, Ma J, Zhou J, Yin M, Wang X, Zhao R, Qiu T, Hou X, Li M","journal":"Food chemistry","year":"2026","volume":"532","issue":"Pt 4","pages":"151735","doi":"10.1016/j.foodchem.2026.151735","url":"https://pubmed.ncbi.nlm.nih.gov/42956604/","species":"rodent","speciesRaw":"rodent","design":"parallel (4 groups)","n":"24 (4 groups x 6, as stated)","status":"complete","statusNote":"Rat oral PK (serum) of silymarin vs liposome vs microencapsulated nanoparticle, with i.v. reference; in vitro release and solubility also reported.","conclusion":"In vivo studies confirmed enhanced bioavailability and safety of SLM-NMP.","limitations":"small n (6); female rats only; large SD for SLM-LIP AUC; IV reference is SLM-NMP, not free SLM; serum vs blood labelling; AUC units printed ng/h/mL"}},"rejected":[{"pmid":"11883719","status":"not absorption-related","note":"Anticancer pharmacodynamic study (A2780 cell growth, apoptosis, nude mouse xenografts, Matrigel angiogenesis) of silybin and IdB 1016 with cisplatin; whole paper read, no plasma/tissue concentration, absorption or PK data reported (bioavailability only mentioned in Introduction/Discussion with references to other studies)"},{"pmid":"17548790","status":"review/non-primary","note":"Narrative review of milk thistle nomenclature/chemistry and previously published pharmacokinetic studies (Kroll, Shaw, Oberlies, Integr Cancer Ther 2007); no original absorption data."},{"pmid":"19041708","status":"review/non-primary","note":"Review article (J Ethnopharmacol 2009) on pharmacokinetic drug-drug interactions of silymarin; no original absorption data. Page 1 (abstract, contents) read; article labelled 'Review'."},{"pmid":"20523105","status":"off-target analyte","note":"PK study of paclitaxel (oral and IV) in rats with oral silibinin as pretreatment; silibinin plasma levels were not measured. Paclitaxel PK values not extracted."},{"pmid":"20828605","status":"not absorption-related","note":"In vitro CYP inhibition/induction and hepatocyte cytotoxicity study of a milk thistle dry extract (HEPAR-PASCO) in human hepatocytes and liver microsomes. No absorption or PK measurements; plasma Cmax values (1.4 and 1.15 ug/ml silibinin) are cited from other literature, not measured."},{"pmid":"21031623","status":"not absorption-related","note":"Pharmacodynamic/efficacy study of silymarin on serum TNF-alpha and haemoglobin in peritoneal dialysis patients; no silymarin/silybin concentrations, PK or absorption parameters measured."},{"pmid":"21656362","status":"not absorption-related","note":"Hepatoprotective efficacy of silymarin nanoemulsion vs standard silymarin suspension against CCl4 hepatotoxicity in rats (serum enzymes, tissue GSH/TBARS, histology). No plasma/tissue silymarin concentrations, PK or absorption data reported."},{"pmid":"22172604","status":"off-target analyte","note":"PK study measured plasma paclitaxel (a drug) in rats; silymarin was given only as a P-gp inhibitor co-administered orally and silymarin/silibinin itself was not measured. Data sections skipped."},{"pmid":"23067546","status":"not absorption-related","note":"In vitro toxicology study of silymarin (2.4 mg/ml) protecting human PBMC against benzo(a)pyrene (ROS, DNA damage, apoptosis, intracellular calcium, CYP1A1/1B1 activity). No absorption or pharmacokinetic measurements. Data sections skipped."},{"pmid":"23205514","status":"off-target analyte","note":"Rat PK study measuring plasma risperidone and 9-hydroxyrisperidone; silymarin (40 mg/kg, single or repeated 5 days) was given only as a P-gp inhibitor and silymarin itself was not measured. Data sections skipped."},{"pmid":"23401473","status":"not absorption-related","note":"In vitro OATP transporter inhibition study (IC50 of silymarin flavonolignans on OATP1B1/1B3/2B1-mediated uptake of E217G, E1S and rosuvastatin in cell lines and human hepatocytes). Measured analytes are radiolabelled probe substrates; no absorption/PK of silymarin measured. Table 3 portal vein concentrations are authors' calculations from literature Cmax (Hawke 2010) and rat Fa, not measured here. Data sections skipped."},{"pmid":"24251357","status":"off-target analyte","note":"PK study of acetaminophen (APAP) and APAP glucuronide in rats; silibinin was given orally as a pretreatment (with NAC) but silibinin itself was not measured in any matrix."},{"pmid":"25544390","status":"not absorption-related","note":"Hepatoprotection study (D-GalN/TNF-alpha liver injury in mice; histology and Bcl-2/Bax/PCNA immunohistochemistry) of silymarin vs silymarin-loaded solid lipid nanoparticles. No plasma/tissue concentrations, PK parameters or absorption measurements. Only formulation particle size and zeta potential reported; bioavailability is mentioned only as a hypothesis."},{"pmid":"26068528","status":"not absorption-related","note":"Rat pharmacodynamic study (plasma/liver lipids, hepatic CYP7A1, CYP4A, ABCG5/8 protein expression) of dietary 1% standardized, micronized and phytosome silymarin; no silymarin/silybin concentration, PK or absorption measurement. Bioavailability differences are only cited from other work."},{"pmid":"26433256","status":"not absorption-related","note":"In vitro radioprotection study of nano-silymarin (SNEDDS) in HEK cells (plasmid relaxation, MTT, micronucleus, ROS, cell cycle) and formulation characterization; no absorption/PK measurement. Bioavailability is mentioned only as rationale."},{"pmid":"26681893","status":"not absorption-related","note":"Physicochemical shelf-life/stability study of a silymarin nanoemulsion at 5, 25 and 40 C over 90 days (HPTLC silybin content, droplet size, viscosity). No absorption or pharmacokinetic data reported."},{"pmid":"26875177","status":"off-target analyte","note":"Measures serum Cu, Zn and Mn in tamoxifen-treated rats given aqueous milk thistle seed extract (1.6 g/kg/day gavage, 14 days); no silymarin/silybin or milk-thistle compound was measured, so no absorption/PK of the supplement."},{"pmid":"27517806","status":"review/non-primary","note":"Narrative review (Eur J Med Chem) of silibinin pharmacokinetics, bioavailability, clinical effects and signalling pathways; not a primary study."},{"pmid":"28602600","status":"off-target analyte","note":"PK study of oxcarbazepine (OXC) and its metabolite licarbazepine (LIC) in rats after i.p. pre-treatment with silymarin, EPG or silymarin/EPG as P-gp inhibitors. Silymarin/silybinin was not measured in plasma or brain; only OXC and LIC were assayed. No silymarin absorption data to extract."},{"pmid":"28643437","status":"off-target analyte","note":"PK drug-interaction study in rats: silibinin (oral, single or 14-day multiple dose) given before oral methadone; only methadone and its metabolite EDDP were measured in plasma. Silibinin concentrations were not measured, so no silibinin absorption data to extract."},{"pmid":"29125572","status":"review/non-primary","note":"Narrative review of silybin chemistry, metabolism and bioavailability (Bijak, Molecules 2017); no original pharmacokinetic data. Pages 1-4 read; publication type listed as Review."},{"pmid":"29710546","status":"not absorption-related","note":"In vitro drug-interaction study: inhibition of CYP2C9-mediated diclofenac 4'-hydroxylation (IC50 approx. 13 uM diosmetin, 33 uM warfarin, 45 uM silibinin) and albumin binding/warfarin displacement by diosmetin and silibinin (fluorescence, ultrafiltration, docking). No absorption, bioavailability or in vivo PK of silibinin is measured; pages 1-4 read."},{"pmid":"29755356","status":"review/non-primary","note":"Narrative review (Frontiers in Pharmacology, 2018) of silymarin in Parkinson's disease; not a primary absorption study. Abstract mentions low bioavailability (23-47%) as a secondary statement only."},{"pmid":"30080294","status":"review/non-primary","note":"Narrative review (Phytotherapy Research, 2018) of milk thistle chemistry, pharmacokinetics and liver-disease uses; not a primary study."},{"pmid":"30795809","status":"review/non-primary","note":"Correction notice (author given/family name tagging error) for the original article BMC Pharmacol Toxicol 2019;20:5 on silybin-phosphatidylcholine vs silymarin tablets. Contains no data."},{"pmid":"31020859","status":"off-target analyte","note":"Silymarin (25 mg/kg, ip) was given as pretreatment (P-gp inhibitor); the measured analytes are the antiepileptic drugs carbamazepine, oxcarbazepine/licarbazepine and phenytoin (and metabolites) in rat plasma/brain. Silymarin/silybin concentrations were not measured, so no silymarin absorption data. Data sections not extracted."},{"pmid":"31035343","status":"off-target analyte","note":"Herb-drug interaction: silymarin (45 mg/kg oral, 7 days) was the perpetrator; measured analytes are simvastatin and simvastatin acid in rat plasma. Silymarin/silybin concentrations were not measured, so no silymarin absorption data. Data sections not extracted."},{"pmid":"31047898","status":"not absorption-related","note":"Efficacy/pharmacology study of oral silymarin (50, 200, 300 mg/kg, 5 days) against radiocontrast-induced nephropathy in mice (renal function, oxidative stress, apoptosis, histology). No silymarin/silybin concentration or other PK/absorption measurement."},{"pmid":"31181687","status":"review/non-primary","note":"Narrative review of formulation strategies for silymarin bioavailability (Molecules 2019;24:2155); secondary source, no original data extracted. Underlying primary studies should be extracted from their own papers."},{"pmid":"31340181","status":"review/non-primary","note":"Narrative review of silibinin nanoformulations (Nanomedicine 2019); no primary PK data"},{"pmid":"31615114","status":"review/non-primary","note":"Narrative review of silymarin metabolism, transport and drug-drug interactions (Molecules 2019); no primary PK data"},{"pmid":"32877720","status":"review/non-primary","note":"Narrative review of Silybum marianum phytochemistry, ethnopharmacology and clinical evidence; no primary absorption data extracted."},{"pmid":"33447529","status":"review/non-primary","note":"Narrative review (J Clin Transl Hepatol) of silymarin in chronic liver disease; no primary absorption data extracted."},{"pmid":"33587317","status":"review/non-primary","note":"Systematic review of published pharmacokinetics and PK interactions of silymarin flavonolignans; secondary source, no primary data extracted."},{"pmid":"33706132","status":"not absorption-related","note":"In vitro study of silymarin flavonolignans and their sulfate metabolites binding to human serum albumin (logKSV, logK; Table 1) and inhibiting CYP2C9/2C19/2D6/3A4 (IC50; Table 2). No absorption, bioavailability or plasma PK data; data sections skipped per rule 10. Reviewer may wish to re-classify as a PK-interaction paper."},{"pmid":"34172076","status":"review/non-primary","note":"Published erratum (1 page) correcting a unit in the Results sentence of Méndez-Sánchez et al. BMC Pharmacol Toxicol 2019;20:5 (doi 10.1186/s40360-018-0280-8). The original article, not this notice, holds the data. The correction states SIB peak plasma concentrations were 207.1 ng/L for SPC and 12.6 ng/L for SM tablets (original printed mg/L)."},{"pmid":"34285784","status":"not absorption-related","note":"Retracted article (Hindawi retraction notice on PDF p.1: peer review compromised, retracted Nov 2022) bundled with the original paper. The paper reports silybin hepatoprotection in CCl4 mice (serum ALT/AST, NF-kB, NO, mortality); no silybin concentration, PK or bioavailability data. 'Absorption promotion' in the title refers to a small-intestinal food retention rate in the model group (p = 0.024), not absorption of silybin."},{"pmid":"35651070","status":"review/non-primary","note":"Narrative review (PubMed type: Review) of nanostructured delivery systems for silymarin; no primary PK data extracted."},{"pmid":"36343684","status":"not absorption-related","note":"In vitro enzyme-inhibition study (silybin A/B inhibition of recombinant UGT1A1*1/*6-catalysed SN-38 glucuronidation; IC50/Ki) with model-predicted herb-drug interaction ratios. No absorption/PK measurements by the authors; Table 2 reproduces literature plasma Cmax of silybins from other studies."},{"pmid":"36381105","status":"not absorption-related","note":"Efficacy study: longitudinal MRI and serum/histology biomarkers of silymarin (100 mg/kg i.p., 3x/week) in thioacetamide-induced rat liver injury. No silymarin concentration, absorption or PK measurement; AUCtmax refers to Gd-EOB-DTPA MRI enhancement, not silymarin."},{"pmid":"36475008","status":"review/non-primary","note":"Retraction notice (1 page) for 'Liver Protection Mechanism and Absorption Promotion Technology of Silybin Based on Intelligent Medical Analysis' (Yan & Zhang, J Healthcare Eng 2021, 9968016), retracted because the peer review process was compromised. Not the original paper; no data."},{"pmid":"38353369","status":"review/non-primary","note":"Narrative review (Phytotherapy Research) on silibinin targeting CD44+ cancer stem cells; PubMed publication type Review. Not a primary absorption/PK study."},{"pmid":"39221555","status":"not absorption-related","note":"Efficacy RCT of silymarin 240 mg every 12 h and/or cholecalciferol 50,000 IU/wk on BPH lower urinary tract symptoms (IPSS, Qmax, prostate volume, PVR, PSA). No silymarin absorption or PK data; serum 25-(OH) vitamin D is only reported as a cholecalciferol/stratification variable."},{"pmid":"39310970","status":"review/non-primary","note":"Narrative review (Phytotherapy Research) of silybin formulations and targeted delivery for liver diseases; PubMed publication type Review. Not a primary absorption/PK study."},{"pmid":"39444787","status":"review/non-primary","note":"Narrative review (Drug Des Devel Ther 2024) of silibinin bioavailability strategies and liver disease; no primary PK data. Data sections skipped."},{"pmid":"39596784","status":"review/non-primary","note":"Narrative review (Antibiotics 2024) of silybin antibacterial, antifungal, antiviral and antiparasitic activity; not an absorption/PK primary study. Data sections skipped."},{"pmid":"40006559","status":"not absorption-related","note":"Formulation development and physicochemical characterisation of silibinin nanoemulsions (solubility in excipients, phase diagrams, particle size, rheology, QCM-D mucoadhesion, surface tension). No PK, permeation, release or absorption measurements. Data sections skipped."},{"pmid":"40158557","status":"not absorption-related","note":"Anticancer efficacy study of silymarin loaded in a Sul-IRMOF-ACA-HA metal-organic framework (CT-26 cells, intratumoral injection in BALB/c mice, oxidative stress markers). Only in vitro cumulative release (UV, dialysis) and loading efficiency are reported; no plasma/tissue PK or permeation data. Data sections skipped."},{"pmid":"41156530","status":"review/non-primary","note":"Narrative review (Nutrients 2025, 17, 3278) of silymarin chemistry, pharmacokinetics and hepatoprotection in porcine models; not a primary PK study. Data sections skipped per rules."},{"pmid":"41196338","status":"not absorption-related","note":"Efficacy study in oxytetracycline-induced MASLD rats (silymarin vs silymarin-piperine-lecithin phytocomplex vs fenofibrate, 90 days; ALT/AST/lipids/histology/PPAR-alpha). No plasma/tissue silymarin concentrations or PK parameters measured; authors list absence of pharmacokinetic and bioavailability assessments as a limitation."},{"pmid":"41394134","status":"review/non-primary","note":"Review article (Front. Pharmacol. 2025, 16:1711653) on silymarin mechanisms, pharmacokinetics, formulation strategies and pre-clinical applications; not a primary study. Data sections skipped per rules."},{"pmid":"41406786","status":"not absorption-related","note":"Medicinal chemistry/in vitro paper: synthesis of silybin-carnosine phosphodiester conjugates (SilpCar) and antioxidant (DPPH, ORAC) and cytoprotective effects in LPS-treated RAW264.7 macrophages. No absorption or PK data; only qualitative serum stability of the conjugates (unchanged over 24 h, data in Supporting Information S43, not in the PDF)."},{"pmid":"41471139","status":"review/non-primary","note":"Review article (Pharmaceutics 2025, 17, 1628) of silymarin/silybin pharmacokinetic barriers and delivery strategies; not a primary study. Data sections skipped per rules."},{"pmid":"42054809","status":"review/non-primary","note":"Narrative review of silibinin and the redox-onco axis (Pathology - Research and Practice 283, 156495); not a primary absorption/PK study."},{"pmid":"42190474","status":"not absorption-related","note":"Hepatoprotective efficacy study of silymarin@ZIF-8 vs conventional silymarin in CCl4-intoxicated broilers; outcomes are body/liver weight, hematology, liver enzymes, oxidative markers, histopathology, comet assay. No silymarin concentration/PK/absorption measured; bioavailability is only inferred by the authors from efficacy."},{"pmid":"42235156","status":"not absorption-related","note":"Protective-efficacy study of Sil@CME@ZIF-8 vs silymarin against CCl4-induced toxicity in brain, spleen and intestine of broiler chicks (organ weights, oxidative markers, histopathology, comet assay). No silymarin concentration/PK/absorption measured; authors state PK and bioavailability data are lacking."},{"pmid":"42785882","status":"off-target analyte","note":"Oral absorption/PK study of doxorubicin (DOX) delivered in pyrimidine nucleoside-chitosan-silybin (PYN-CS-SB) micelles; silybin is a polymer-conjugated P-gp/CYP3A4 inhibitor and its own concentration, release or absorption was not measured. PK analyte is DOX (e.g. 391% relative oral bioavailability of DCD-CS-SB@DOX vs DOX.HCl)."},{"pmid":"42892542","status":"off-target analyte","note":"Herb-drug interaction PK study: resmetirom plasma PK and microsomal stability in MCD-diet MASH rats with/without milk thistle supplement. Only resmetirom was quantified in plasma; silybin A+B was quantified only as supplement content (HPLC standardization), not absorbed silybin."}],"indirect":[{"anchor":"indirect-silymarin-vs-phytosome","a":"silymarin","b":"phytosome","aLabel":"Standard silymarin extract","bLabel":"Silybin phytosome (silybin-phosphatidylcholine)","label":"Indirect comparison","baseline_nr":true,"grade":"D","grade_basis":"non-overlapping ranges but <2 studies per form (single-study ranges); uses value(s) with baseline correction not reported (capped at C under rubric v2)","head_to_head_grade":"C","note":"Head-to-head evidence exists and takes precedence over this indirect comparison.","status":"draft — pending reviewer (Dr. Colin Reily)","comparisons":[{"parameter":"Cmax","analyte":"silybin a","matrix":"serum/plasma","fed":"fasted","dosing":"single","auc_interval":"","baseline_corrected":"not reported","units":"ng/ml","baseline_nr":true,"label":"baseline correction not reported","basis":"values as printed (doses not normalized)","a":{"n_studies":1,"n_values":1,"total_n":12,"range":[15.69,15.69],"per_mg_range":null,"values":[{"pmid":"29273470","value":"15.69","units":"ng/ml","dose":"2 capsules (one serving) capsules","dose_basis":"NR","n":"12","arm":"","location":"Table III","per_mg":null}]},"b":{"n_studies":1,"n_values":1,"total_n":22,"range":[2333.7,2333.7],"per_mg_range":null,"values":[{"pmid":"18054294","value":"2333.7","units":"ng/ml","dose":"280 mg silybin (133 mg silybin A + 147 mg silybin B)","dose_basis":"active compound","n":"22","arm":"","location":"Table 3","per_mg":null}]},"higher":"phytosome","separated":true,"pmids":["18054294","29273470"]},{"parameter":"Cmax","analyte":"silybin b","matrix":"serum/plasma","fed":"fasted","dosing":"single","auc_interval":"","baseline_corrected":"not reported","units":"ng/ml","baseline_nr":true,"label":"baseline correction not reported","basis":"values as printed (doses not 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(cross-study) PK comparisons from bundle_v2 single-form human arms.\nValues are copied as printed. Matching key: parameter, analyte, matrix, fed/fasted, single vs repeated,\nAUC interval (from parameter_detail), baseline correction, units (exact). No pooling/averaging: per-form\nranges are min–max of printed values. Analyte for minerals/B12 is classed as total element vs isotope/radiotracer; units compared after removing spaces/separators only; IV arms excluded; serum and plasma treated as the same matrix; curated magnesium v1 rows (mapped from stated conditions only, NR otherwise, deduped against the bundle) are included; baseline correction NR is treated as unknown (may match corrected or uncorrected sets; labeled and capped at C); for % absorption endpoints an unreported baseline correction is treated as not applicable. Normalization: value / elemental dose (mg) ONLY when dose_basis is\n'elemental', dose unit is mg, single dose, baseline-corrected=yes, parameter Cmax/AUC. Grade capped at C.\nRun after merge_bundle.py.","formGrades":{"silymarin":{"label":"Standard silymarin extract","grade":"C","basis":"11 human studies, total n=119, 7 randomized/crossover; median CV 102.85% across 2 matched set(s) (inconsistent)","studies":11,"total_n":119,"randomized":7,"median_cv":102.85,"cv_sets":[{"set":"Cmax / silybin / serum/plasma / fasted / single /  / ng/ml","studies":["30635055","39204378"],"cv":133.4},{"set":"Tmax / silybin / serum/plasma / fasted / single /  / h","studies":["30635055","39204378"],"cv":72.3}],"pmids":["16278402","18566043","19841158","21865319","23835761","26595166","26642669","29273470","30635055","39204378","40733088"]},"phytosome":{"label":"Silybin phytosome (silybin-phosphatidylcholine)","grade":"B","basis":"3 human studies, total n=65, 1 randomized/crossover; median CV 17.0% across 1 matched set(s) (consistent)","studies":3,"total_n":65,"randomized":1,"median_cv":17,"cv_sets":[{"set":"Tmax / silybin / serum/plasma / fasted / single /  / h","studies":["17315537","30635055"],"cv":17}],"pmids":["17315537","18054294","30635055"]},"enhanced":{"label":"Other enhanced formulas (SMEDDS, micellar, water-soluble)","grade":"B","basis":"4 human studies, total n=56, 2 randomized/crossover; consistency not evaluable (no matched set with ≥2 studies)","studies":4,"total_n":56,"randomized":2,"median_cv":null,"cv_sets":[],"pmids":["23072776","30108644","39204378","40733088"]}},"headlineGrade":"B","rubric":"Rubric v2 (draft, pending reviewer): single-form human studies count.\n(1) Per-form 'absorption evidence' grade from human PK/absorption values of single-form arms:\n    studies, total n, design (randomized/crossover share), consistency = CV of per-study medians within\n    matched condition sets (same parameter, analyte, matrix [serum=plasma], fed, dosing, AUC interval, units; >=2 studies).\n    A: >=5 studies, total n >=100, >=2 randomized/crossover, and no evidence of inconsistency\n       (median CV <=100% across matched sets, or not evaluable because no matched set has >=2 studies; this is reported).\n    B: >=3 studies (or 2 studies with consistent matched values). C: 1-2 studies. D: animal/in vitro only.\n    Median CV <=50% = consistent; 50-100% = heterogeneous (reported, not penalized: dose, iron status and\n    population differ between studies); >100% = inconsistent, grade lowered one step.\n(2) Per pair: combine head-to-head (H2H) grade with matched single-form (indirect) evidence.\n    Indirect direction = form favored in matched sets whose ranges do not overlap (Tmax excluded).\n    Strong indirect: separated set(s) with >=3 studies per form (A-capable) or >=2 (B-capable), no contradicting set.\n    A: strong indirect (>=3/form) agreeing with H2H or no H2H, or H2H A not contradicted.\n    Conflict between H2H and indirect direction: one step below the better of the two (min D).\n    Comparisons using values with baseline correction not reported are capped at C.\nValues are never computed into new estimates: CV is used only as a consistency check and is shown with its inputs.","headlineBasis":"best grade across this page's form absorption grades and 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information about published research; not medical advice. Not intended to diagnose, treat, cure or prevent any disease. Talk to a clinician before changing supplements, especially if pregnant, nursing or on medication.","last_reviewed":null,"page_url":"https://supplementabsorption.com/milk-thistle?utm_source=chatgpt"}