PT  - JOURNAL ARTICLE
AU  - Zhiming Wen
AU  - Todd E. Dumas
AU  - Sarah J. Schrieber
AU  - Roy L. Hawke
AU  - Michael W. Fried
AU  - Philip C. Smith
TI  - Pharmacokinetics and Metabolic Profile of Free, Conjugated, and Total Silymarin Flavonolignans in Human Plasma after Oral Administration of Milk Thistle Extract
AID  - 10.1124/dmd.107.017566
DP  - 2008 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 65--72
VI  - 36
IP  - 1
4099  - http://dmd.aspetjournals.org/content/36/1/65.short
4100  - http://dmd.aspetjournals.org/content/36/1/65.full
SO  - Drug Metab Dispos2008 Jan 01; 36
AB  - Silymarin, a mixture of polyphenolic flavonoids extracted from milk thistle (Silybum marianum), is composed mainly of silychristin, silydianin, silybin A, silybin B (SBB), isosilybin A (ISBA), and isosilybin B. In this study, the plasma concentrations of free (unconjugated), conjugated (sulfated and glucuronidated), and total (free and conjugated) silymarin flavonolignans were measured using liquid chromatography-electrospray ionization-mass spectrometry, after a single oral dose of 600 mg of standardized milk thistle extracts to three healthy volunteers. Pharmacokinetic analysis indicated that silymarin flavonolignans were rapidly eliminated with short half-lives (1–3 and 3–8 h for free and conjugated, respectively). The AUC0→∞ values of the conjugated silymarin flavonolignans were 4- to 30-fold higher than those of their free fractions, with SBB (mean AUC0→∞ = 51 and 597 μg · h/l for free and conjugated, respectively) and ISBA (mean AUC0→∞ = 30 and 734 μg · h/l for free and conjugated, respectively) exhibiting higher AUC0→∞ values in comparison with other flavonolignans. Near the plasma peak times (1–3 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. The American Society for Pharmacology and Experimental Therapeutics