Interaction Between Clopidogrel And Proton Pump Inhibitors Based On Polymorphisms Of Cyp450

We identify the genotype and allele distribution feature of cytochrome P450 2C19 (CYP2C19) in Chinese Hui,Zang and Han populations from Gansu area, and investigate the effects of gender on genetic polymorphism of CYP2C19 in these populations. The CYP2C19 genotypes of the unrelated healthy Chinese Hui,Zang and Han population subjects were assessed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Six different CYP2C19 genotypes were observed in this study. There was no significant difference between male and female, but significant difference among three Chinese populations (P<0.05). Population has significant effect on genetic polymorphism of CYP2C19 in Chinese Hui,Zang and Han populations from Gansu area, and gender hasn't.Using of omeprazole to significantly decrease the clopidogrel antiplatelet effect because of cytochrome P450 interaction. Because all PPIs are metabolized by CYP2C19, but to a varying degree, we hypothesized that the reported negative omeprazole–clopidogrel drug interaction may not be caused by a class effect. On the bases of method for genotyping of CYP2C19 and the CYP2C19 polymorphisms of the major populations in Gansu area, this study sought to investigate the effect of the CYP2C19 polymorphisms on platelet response to clopidogrel with 2 proton pump inhibitors (PPIs) (omeprazole and pantoprazole) after coronary stenting for non–ST-segment elevation acute coronary syndrome (NSTE ACS). A total of 241 or 232 patients undergoing coronary stenting for NSTE ACS were prospectively included and taken omeprazole or pantoprazole 20 mg. They received at discharge 100-mg aspirin and 75-mg clopidogrel. Platelet reactivity index (PRI) vasoactive stimulated phosphoprotein (VASP) was used to assess clopidogrel response and adenosine diphosphate (ADP)–induced aggregation for platelet reactivity (ADP-Ag). After 1 month, patients belonging to EMhomo group had a significantly better platelet response to clopidogrel as assessed with the PRI VASP: 36±20%versus50±17% (p =0.007). We identified more clopidogrel nonresponders in the PM group than in the EMhomo group: 44%versus23%(p=0.04), odds ratio: 2.6 (95% confidence interval: 1.2 to 6.2). Similly, we observed significant difference in platelet reactivity with ADP-Ag between the EMhomo and PM groups:42.2±18% and 62.7±15%, respectively(p=0.04). The present findings suggest the preferential use of pantoprazole compared with omeprazole in patients receiving clopidogrel to avoid any potential negative interaction with CYP2C19.