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Clopidogrel Inhibits CYP2C19‐Dependent Hydroxylation of Omeprazole Related to CYP2C19 Genetic Polymorphisms
Author(s) -
Chen B. L.,
Chen Y.,
Tu J. H.,
Li Y. L.,
Zhang W.,
Li Q.,
Fan L.,
Tan Z. R.,
Hu D. L.,
Wang D.,
Wang L. S.,
OuYang D. S.,
Zhou H. H.
Publication year - 2009
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009333016
Subject(s) - omeprazole , cyp2c19 , clopidogrel , pharmacokinetics , pharmacology , crossover study , proton pump inhibitor , medicine , cyp3a4 , placebo , chemistry , aspirin , metabolism , cytochrome p450 , alternative medicine , pathology
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 AUC 0–∞ 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 AUC 0–∞ 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.