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Clopidogrel Inhibits CYP2C19-Dependent Hydroxylation of Omeprazole Related to CYP2C19 Genetic Polymorphisms.
- Source :
-
Journal of Clinical Pharmacology . May2009, Vol. 49 Issue 5, p574-581. 8p. 1 Chart, 2 Graphs. - Publication Year :
- 2009
-
Abstract
- This study explores the impact of clopidogrel on the pharmacokinetics of omeprazole related to CYP2C19 genetic polymorphisms. Twelve healthy volunteers (6 CYP2C19*1/ *1, 5 CYP2C19*2/*2, and 1 CYP2C19*2/*3) are enrolled in a 2-phase randomized crossover trial. In each phase, the volunteers are administered a single oral dose of omeprazole 40 mg after pretreatment of either placebo or clopidogrel (300 mg on the first day and then 75 mg once daily for 3 consecutive days). Plasma concentrations of omeprazole and its metabolites are quantified by high-performance liquid chromatography with UV detection. After clopidogrel treatment, the AUC0-∞ of omeprazole increases by 30.02% ± 18.03% (P = .004) and that of 5-hydroxyomeprazole decreases by 24.30% ± 11.66% (P = .032) in CYP2C19*1/*1. The AUC0-∞ ratios of omeprazole to 5-hydroxyomeprazole increase by 74.98% ± 35.48% (P = .001) and those of omeprazole to omeprazole sulfone do not change significantly (P = .832) in CYP2C19*1/*1. No significant alteration is observed in CYP2C19*2/*2 or *3. Clopidogrel inhibits CYP2C19-dependent hydroxylation of omeprazole in CYP2C19*1/*1 and has no impact on CYP3A4-catalyzed sulfoxidation of omeprazole. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00912700
- Volume :
- 49
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 39773573
- Full Text :
- https://doi.org/10.1177/0091270009333016