Incidence of drug interaction when using proton pump inhibitor (PPI) and warfarin according to cytochrome P-450 (CYP) 2C19 genotype in Japanese

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The US Food and Drug Administration has suggested that proton pump inhibitors (PPI)increase the international normalized ratio(INR) when used concomitantly with warfarin(WF), because of being metabolized by cytochrome P450(CYP)2C19. We assessed whether CYP2C19 genotypes and type of PPI accentuated the drug interaction. The study group was 82 patients who needed WF after surgery and had their CYP2C19 genotypes analyzed in advance. We randomly divided them into two groups: Group I(n=41) who had lansoprazol, and Group II(n=41) who had rabeprazole. Bleeding events complicated 10 patients in Group I, but none in Group II. Logistic regression analysis revealed that over-INR, and pair of lansoprazole and CYP2C19 intermediate metabolizer were independent predictors of bleeding events. If a patient had has the intermediate metabolizer CYP2C19 genotype and concomitant use of WF and a PPI after open heart surgery, lansoprazole intensifies the effects of WF and is associated with bleeding events.