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

根据日本细胞色素 P-450 (CYP) 2C19 基因型，使用质子泵抑制剂 (PPI) 和华法林时药物相互作用的发生率

• 批准号: 23592049
• 负责人: HATA Mitsumasa
• 金额: $ 0.42万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592049/
• 关键词: ゲノム創薬; 抗凝固療法; 薬剤相互作用; 薬剤代謝酵素; 開心術後出血合併症; ゲノム; 薬剤反応性

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.

美国食品药品监督管理局提出，与WARFARIN（WF）一起使用时，质子泵抑制剂（PPI）会增加国际标准化比率（INR），因为被细胞色素P450（CYP）2C19代谢。我们评估了CYP2C19基因型和PPI类型是否突出了药物相互作用。研究组是82例，他们需要在手术后需要WF，并提前对其CYP2C19基因型进行了分析。我们将它们随机分为两组：I组（n = 41），患有兰索拉唑，第二组（n = 41）患有Rabeprazole。出血事件使I组的10例患者复杂化，但在第二组中没有。逻辑回归分析表明，过度inr，一对兰索拉唑和CYP2C19中间代谢剂是出血事件的独立预测指标。如果患者患有中间代谢剂CYP2C19基因型，并在心脏病手术后伴随使用WF和PPI，则兰索拉唑会增强WF的作用，并与出血事件有关。