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

美国食品药品监督管理局（FDA）建议，质子泵抑制剂（PPI）与华法林（WF）同时使用时会增加国际标准化比值（INR），因为它会被细胞色素P450（P450）2C19代谢。我们评估了CYP2C19基因型和PPI类型是否加重了药物相互作用。研究组为82例手术后需WF的患者，并预先进行CYP2C19基因型分析。我们将他们随机分为两组：第一组（n=41），服用兰索拉唑，第二组（n=41），服用雷贝拉唑。第I组中有10例患者发生出血事件并发症，但第II组中无一例。Logistic回归分析显示，过高的INR、兰索拉唑和CYP2C19中间代谢物配对是出血事件的独立预测因素。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合并使用WF和PPI，兰索拉唑会加重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.