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Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract.
Drug Metab Dispos. 2008 Jan; 36(1):65-72.DM

Abstract

Silymarin, a mixture of polyphenolic flavonoids extracted from milk thistle (Silybum marianum), is composed mainly of silychristin, silydianin, silybin A, silybin B (SB(B)), isosilybin A (ISB(A)), 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 AUC(0-->infinity) values of the conjugated silymarin flavonolignans were 4- to 30-fold higher than those of their free fractions, with SB(B) (mean AUC(0-->infinity) = 51 and 597 microg x h/l for free and conjugated, respectively) and ISB(A) (mean AUC(0-->infinity) = 30 and 734 microg x h/l for free and conjugated, respectively) exhibiting higher AUC(0-->infinity) 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.

Authors+Show Affiliations

School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17913795

Citation

Wen, Zhiming, et al. "Pharmacokinetics and Metabolic Profile of Free, Conjugated, and Total Silymarin Flavonolignans in Human Plasma After Oral Administration of Milk Thistle Extract." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 36, no. 1, 2008, pp. 65-72.
Wen Z, Dumas TE, Schrieber SJ, et al. Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract. Drug Metab Dispos. 2008;36(1):65-72.
Wen, Z., Dumas, T. E., Schrieber, S. J., Hawke, R. L., Fried, M. W., & Smith, P. C. (2008). Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 36(1), 65-72.
Wen Z, et al. Pharmacokinetics and Metabolic Profile of Free, Conjugated, and Total Silymarin Flavonolignans in Human Plasma After Oral Administration of Milk Thistle Extract. Drug Metab Dispos. 2008;36(1):65-72. PubMed PMID: 17913795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract. AU - Wen,Zhiming, AU - Dumas,Todd E, AU - Schrieber,Sarah J, AU - Hawke,Roy L, AU - Fried,Michael W, AU - Smith,Philip C, Y1 - 2007/10/03/ PY - 2007/10/5/pubmed PY - 2008/2/9/medline PY - 2007/10/5/entrez SP - 65 EP - 72 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab. Dispos. VL - 36 IS - 1 N2 - Silymarin, a mixture of polyphenolic flavonoids extracted from milk thistle (Silybum marianum), is composed mainly of silychristin, silydianin, silybin A, silybin B (SB(B)), isosilybin A (ISB(A)), 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 AUC(0-->infinity) values of the conjugated silymarin flavonolignans were 4- to 30-fold higher than those of their free fractions, with SB(B) (mean AUC(0-->infinity) = 51 and 597 microg x h/l for free and conjugated, respectively) and ISB(A) (mean AUC(0-->infinity) = 30 and 734 microg x h/l for free and conjugated, respectively) exhibiting higher AUC(0-->infinity) 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. SN - 1521-009X UR - https://www.unboundmedicine.com/medline/citation/17913795/Pharmacokinetics_and_metabolic_profile_of_free_conjugated_and_total_silymarin_flavonolignans_in_human_plasma_after_oral_administration_of_milk_thistle_extract_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=17913795 DB - PRIME DP - Unbound Medicine ER -