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Drug Metabolism and Drug Interactions

Drug Metabolism and Drug Interactions is the official journal of the European Society of Pharmacogenomics and Theranostics

Editor-in-Chief: Siest, Gérard

Editorial Board Member: Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Henney, Adriano / Hirata, Rosario D. C. / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Llerena, Adrián / Maitland-van de Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Sadee, Wolfgang / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Visvikis-Siest, Sophie / Zanger, Ulrich M.

4 Issues per year

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Clopidogrel pharmacogenetics: metabolism and drug interactions

1Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA

Corresponding author: Sandra L. Close, PhD, Indiana University School of Medicine, Division of Clinical Pharmacology, 11300 Geist Bay Court, Fishers, IN 46040 USA Tel.: +1-317-578-9879, Fax: +1-317-863-5655

Citation Information: Drug Metabolism and Drug Interactions. Volume 26, Issue 2, Pages 45–51, ISSN (Online) 2191-0162, ISSN (Print) 0792-5077, DOI: 10.1515/dmdi.2011.002, August 2011

Publication History

Received:
2011-02-07
Accepted:
2011-06-27
Published Online:
2011-08-05

Abstract

The thienopyridine, clopidogrel bisulfate (clopidogrel), is the most widely prescribed antiplatelet therapy in the world. Clopidogrel, alone or in conjunction with aspirin as part of a dual antiplatelet therapy regimen, is the standard of care for reducing ischemic events in patients with acute coronary syndrome, recent myocardial infarction, recent stroke, or established peripheral artery disease. Initially approved for use in 1997, the label was updated by both the USA Food and Drug Administration and the European Medicines Agency in 2009 to include information regarding cytochrome P450 (CYP) genotype status and concomitant proton pump inhibitor use. Labeling warns of reduced effectiveness in those with impaired CYP2C19 function and to avoid concomitant clopidogrel use with drugs that are strong or moderate CYP2C19 inhibitors, such as omeprazole. The interpretation of this warning and the implementation in clinical practice is not without controversy. The following review provides a summary of the published evidence regarding CYP2C19 function, both genotype status and drug inhibition from concomitant proton pump inhibitors use, and response to clopidogrel.

Keywords: antiplatelet therapy; clopidogrel; CYP2C19; cytochrome P450; proton pump inhibitors

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