Influence of Proton Pump Inhibitors on Efficacy of Clopidogre in Patients with Each Type of CYP2C19 Polymorphism

Abstract

Recent studies carried out in Western countries have suggested a potential adverse interaction between clopidogrel and proton pump inhibitors (PPIs), which inhibit CYP2C19 activity. The purpose of this study was to examine the influence of individual PPIs and CYP2C19 polymorphism on the antiplatelet effect of clopidogrel in Japan. The platelet aggregations induced by 20 μmol/L ADP and CYP2C19 single nucleotide polymorphisms (^*2 and ^*3) were determined in 118 patients on aspirin plus clopidogrel (75 mg/day) therapy. Twenty-five and 13 patients were treated with lansoprazole and rabeprazole, respectively. The platelet aggregation of extensive metabolizers (EM : ^*1/^*1) treated with lansoprazole tended to be higher than those not given a PPI (21.5 % vs. 17.4 %, respectively, p=0.14). Lansoprazole was observed to have no effect on platelet aggregation in intermediate metabolizers (IM : ^*1/^*2 and ^*1/^*3) and poor metabolizers (PM : ^*2/^*2, ^*2/^*3, and ^*3/^*3). Furthermore, platelet aggregation in IMs and PMs not given lansoprazole was significantly higher than that in EMs taking lansoprazole. Rabeprazole did not affect platelet aggregation in any genotype. These results suggest that the influence of PPIs on the antiplatelet effect of clopidogrel is minimal in Japanese patients.