DMD Simcyp

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on August 1, 2007; DOI: 10.1124/dmd.107.016410

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.107.016410v1
35/11/2035    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Author home page(s):
Petra Jancova
Eva Anzenbacherova
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jancova, P.
Right arrow Articles by Simanek, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jancova, P.
Right arrow Articles by Simanek, V.


Received for publication May 18, 2007.
Revised July 29, 2007.
Accepted for publication July 30, 2007.

Silybin is metabolized by cytochrome P450 2C8 in vitro

Petra Jancova 1, Eva Anzenbacherova 1*, Barbora Papouskova 2, Karel Lemr 2, Pavla Luzna 3, Alena Veinlichova 3, Pavel Anzenbacher 4, Vilim Simanek 5

1 Palacky University Fac Medicine Dept Med Chem Biochem 2 Palacky Univ Fac Sciences Dept Anal Chemistry 3 Palacky Univ Fac Medicine Dept Pharmacology 4 Palacky University 5 Palacky Univ Fac Medicine Dept Med Chem Biochem

* Address correspondence to: E-mail: anzeneva{at}tunw.upol.cz

Abstract

Silybin (a flavonolignan, the main component of silymarin, extract from seeds of Silybum marianum) has been used to date mostly as hepatoprotectant showing however also other interesting activities, e.g. anticancer or hypocholesterolemic effects. It is also known that silybin can inhibit activities of the CYP enzymes. In this study, a weak interaction of silybin with human microsomal CYPs 2E1, 2A6, 2B6, 2C19 and 2D6 (IC50 ≥ 250 µM) was found; a moderate inhibition was observed for CYPs 1A2 and 2C8. The most prominent inhibition effect was found with CYP3A4 and CYP2C9 (IC50 ≤ 50 µM). Using the MS detection, production of O-demethylated (the main metabolite) as well as of the hydroxylated derivatives of silybin formed by CYP enzymes was detected. The effect of different CYP inhibitors on the formation of O-demethylated product was also studied. In particular, a relatively specific inhibitor of the CYP2C8 (quercetin) markedly inhibited the formation of this metabolite. With the help of recombinant enzymes (bactosomes) it was confirmed that it is the CYP2C8 enzyme which is responsible for the reaction leading to the O-demethylated silybin.


Key words: CYP2C, drug interactions, human CYP enzymes, metabolite identification


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
S. R. Miranda, J. K. Lee, K. L. R. Brouwer, Z. Wen, P. C. Smith, and R. L. Hawke
Hepatic Metabolism and Biliary Excretion of Silymarin Flavonolignans in Isolated Perfused Rat Livers: Role of Multidrug Resistance-Associated Protein 2 (Abcc2)
Drug Metab. Dispos., November 1, 2008; 36(11): 2219 - 2226.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2007 by the American Society for Pharmacology and Experimental Therapeutics.