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

美国食品和药物管理局建议质子泵抑制剂（PPI）与华法林（WF）联合使用时，由于被细胞色素P450(CYP)2C19代谢，可增加国际标准化比率（INR）。我们评估了CYP2C19基因型和PPI类型是否加剧了药物相互作用。研究组为82例术后需要WF并提前分析其CYP2C19基因型的患者。我们将他们随机分为两组：第一组（n=41）使用兰索拉唑，第二组（n=41）使用雷贝拉唑。1组有10例合并出血事件，2组无出血事件。Logistic回归分析显示，inr过高、兰索拉唑和CYP2C19中间代谢物对是出血事件的独立预测因子。如果患者具有中间代谢物CYP2C19基因型，并且在心脏直视手术后同时使用WF和PPI，则兰索拉唑会加强WF的作用，并与出血事件相关。

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.