Key result
Clopidogrel increased the AUC of omeprazole by 30.02% (P=0.004) in healthy volunteers with the CYP2C19*1/*1 genotype, but had no significant effect in those with *2/*2 or *3 genotypes.
Why the study?
Does clopidogrel alter the pharmacokinetics of omeprazole in relation to CYP2C19 genetic polymorphisms in healthy volunteers?
RCT (n=12)
crossover
Does clopidogrel alter the pharmacokinetics of omeprazole in relation to CYP2C19 genetic polymorphisms in healthy volunteers?
Effect estimate: 30.02% +/- 18.03% increase
p-value: p=.004
Clopidogrel significantly inhibits the CYP2C19-dependent hydroxylation of omeprazole in individuals with the CYP2C19*1/*1 genotype, demonstrating a genotype-specific pharmacokinetic drug-drug interaction.
Potential for increased omeprazole exposure with clopidogrel in CYP2C19*1/*1 patients; extends evidence of genotype-specific CYP2C19 inhibition.
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-infinity) 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-infinity) 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.
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Chen et al. (2009) conducted an RCT in Healthy volunteers (n=12). Clopidogrel vs. Placebo was evaluated on AUC(0-infinity) of omeprazole in CYP2C19*1/*1 (30.02% +/- 18.03% increase, p=.004). Clopidogrel increased the AUC of omeprazole by 30.02% (P=0.004) in healthy volunteers with the CYP2C19*1/*1 genotype, but had no significant effect in those with *2/*2 or *3 genotypes.
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