Relative Bioavailability of Silybin A and Silybin B From 2 Multiconstituent Dietary Supplement Formulations Containing Milk Thistle Extract: A Single-dose Study

• Published in: Clinical therapeutics Vol. 40; no. 1; pp. 103 - 113.e1
• Main Authors: Li, Wen-Yi, Yu, Guo, Hogan, Renee M., Mohandas, Rajesh, Frye, Reginald F., Gumpricht, Eric, Markowitz, John S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2018; Elsevier Limited
• Subjects: absorption; Administration, Oral; Adult; Aging; Antioxidants; Antioxidants - administration & dosage; Antioxidants - pharmacokinetics; Area Under Curve; Bioavailability; Biological Availability; Capsules; Chromatography, Liquid; Cross-Over Studies; Dietary Supplements; Disease; Disease prevention; Drug Compounding; Drug dosages; Family medical history; Female; formulation; Formulations; Functional foods & nutraceuticals; Gels; Humans; Laboratories; Male; Medical screening; milk thistle; pharmacokinetic properties; Phytochemicals; Plant Extracts - administration & dosage; Plant Extracts - pharmacokinetics; Plasma; Polyphenols; Powders; Pregnancy; Silybin; Silybum; Silybum marianum; Silymarin - administration & dosage; Silymarin - blood; Silymarin - pharmacokinetics; Studies; Tandem Mass Spectrometry; Therapeutic Equivalency; Urine; Womens health; Young Adult; formulation; absorption; milk thistle; pharmacokinetic properties; silybin
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2017.11.013

The purpose of this study was to compare the bioavailability between 2 milk thistle–containing dietary supplements, Product B and IsaGenesis, in healthy volunteers. Bioavailability between Product B, originally formulated as a powdered capsule, and IsaGenesis, reformulated as a soft gel, were compared by measuring silybin A and silybin B as surrogate pharmacokinetic markers for differences in absorption and bioavailability. For this randomized, open-label, crossover pharmacokinetic study, 12 healthy volunteers consumed a single-dose serving of each supplement separated by at least a 7-day washout period. Serial blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours and analyzed via LC-MS/MS. Rapid absorption and elimination of silybin A and silybin B have been observed after oral administration of both Product B and IsaGenesis. However, the absorption rate and extent, as indicated by mean the Cmax and mean plasma AUC, were significantly higher for the IsaGenesis soft gel formulation. The dose-corrected mean Cmax was 365% and 450% greater for silybin A and B, respectively, relative to powdered Product B. The time to Tmax was reached, on average, at least 1 hour earlier with IsaGenesis relative to Product B for both silybin A and silybin B. The IsaGenesis soft gel formulation provided substantially greater absorption and bioavailability of silybin A and silybin B relative to the powdered Product B supplement. ClinicalTrials.gov Identifier: NCT02529605.