Pharmacokinetics and Metabolic Profile of Free, Conjugated and Total Silymarin Flavonolignans in Human Plasma [...].

Pharmacokinetics and Metabolic Profile of Free, Conjugated and Total Silymarin Flavonolignans in Human Plasma after Oral Administration of Milk Thistle Extract.: Drug Metab Dispos. 2007 Oct 3; Authors: Wen Z, Dumas TE, Schrieber SJ, Hawke RL, Fried MW, Smith PC

Silymarin, a mixture of polyphenolic flavonoids extracted from milk thistle (Silybum marianum), is mainly composed of silychristin (SC), silydianin (SD), silybin A (SBA), silybin B (SBB), isosilybin A (ISBA), and isosilybin B (ISBB). In this study, the plasma concentrations of free (unconjugated), conjugated (sulfated and glucuronidated), and total (free and conjugated) silymarin flavonolignans were measured using a liquid chromatography-electrospray ionization-mass spectrometry, after a single oral dose of 600 mg standardized milk thistle extracts to three healthy volunteers. Pharmacokinetic analysis indicated that silymarin flavonolignans were rapidly eliminated with short half-lives (1 to 3 and 3 to 8 h for the free and conjugated, respectively). The AUC0-->infinity values of the conjugated silymarin flavonolignans were 4- to 30-fold higher than those of their free fractions, with SBB (mean AUC0-->infinity = 51 and 597 microg.h/l for the free and conjugated, respectively) and ISBA (mean AUC0-->infinity = 30 and 734 microg.h/l for the free and conjugated, respectively) exhibiting higher AUC0-->infinity values in comparison to other flavonolignans. Near the plasma peak times (1 to 3 h), the free, sulfated, and glucuronidated flavonolignans represented approximately 17, 28, and 55 % of the total silymarin, respectively. In addition, the individual silymarin flavonolignans exhibited quite different plasma profiles for both the free and conjugated fractions. 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.

PMID: 17913795 [PubMed - as supplied by publisher]