【摘要】 目的 探讨CYP2C19基因多态性对氯吡格雷与雷贝拉唑药物相互作用的影响。方法 选取医院2019年10月至2021年5月收治的急性冠状动脉综合征（ACS）患者600例，按随机数字表法分为A组、B组、C组，各200例。3组患者均口服硫酸氢氯吡格雷片300 mg+阿司匹林肠溶片300 mg治疗，并予硫酸氢氯吡格雷片75 mg/d及阿司匹林肠溶片100 mg/d维持治疗。B组患者加服低剂量（10 mg/d）雷贝拉唑钠肠溶片，C组患者加服高剂量（20 mg/d）雷贝拉唑钠肠溶片，均连续治疗1年。采用Pharm GKB代谢分型标准对患者进行基因分型；采用血栓弹力图（TEG）法检测患者入院用药7 d后的二磷酸腺苷（ADP）抑制率、二磷酸腺苷诱导的血小板纤维蛋白凝块强度（MA-ADP）；采用全自动凝血分析仪检测凝血酶原时间、活化部分凝血活酶时间、凝血酶时间及纤维蛋白原水平。治疗期间观察患者主要心血管不良事件（MACE）及胃肠道反应发生情况。结果 3组患者中，快代谢型、中间代谢型、慢代谢型患者分布比例无显著差异（P> 0.05）；与A组比较，B组、C组患者的ADP抑制率显著降低，C组患者的MA-ADP显著升高（P <0.05）；快代谢型患者中，与A组比较，B组、C组患者的ADP抑制率均显著降低，C组患者的MA-ADP显著升高（P <0.05）；中间代谢型患者中，与A组比较，C组患者的ADP抑制率显著降低（P <0.05）。3组患者的MACE及胃肠道反应发生率比较无显著差异（P> 0.05）。结论 CYP2C19基因多态性对氯吡格雷与雷贝拉唑的相互作用有一定影响，临床合用时应加以考虑。更多还原

【Abstract】 Objective To investigate the effect of CYP2C19 gene polymorphisms on drug-drug interactions between clopidogrel and rabeprazole.Methods A total of 600 patients with acute coronary syndrome(ACS) admitted to the hospital from October 2019 to May 2021 were selected and randomly divided into groups A,B and C according to the random number table method,with 200 cases in each group. The patients in the three groups were given Clopidogrel Bisulfate Tablets(300 mg)+ Aspirin Enteric-Coated Tablets(300 mg),and maintenance therapy with Clopidogrel Bisulfate Tablets(75 mg/d) and Aspirin Enteric-Coated Tablets(100 mg/d). On this basis,the patients in group B were treated with low-dose(10 mg/d) of Rabeprazole Sodium Enteric-Coated Tablets and those in group C were treated with high-dose(20 mg/d) of Rabeprazole Sodium Enteric-Coated Tablets. All the groups were treated for one year. The patients’ genotypes were classified by Pharm GKB metabolic typing standard. The inhibition rate of adenosine diphosphate(ADP) and ADP-induced platelet-fibrin clot strength(MA-ADP) were measured by thromboelastography(TEG) on the seventh day after admission. The prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT) and fibrinogen(Fib) level were measured by an automatic coagulation analyzer. The incidence of major adverse cardiovascular events(MACE) and gastrointestinal reactions was observed during treatment.Results There was no significant difference in the distribution ratio of extensive metabolizers(EM),intermediate metabolizer(IM) and poor metabolizer(PM) among the three groups(P > 0. 05). The inhibition rate of ADP in group B and group C was significantly lower than that in group A,while the MA-ADP in group C was significantly higher than that in group A(P < 0. 05). In EM patients,the inhibition rate of ADP in group B and group C was significantly lower than that in group A,while the MA-ADP in group C was significantly higher than that in group A(P < 0. 05). In IM patients,the ADP inhibition rate in group C was significantly lower than that in group A(P < 0. 05). There was no significant difference in the incidence of MACE and gastrointestinal reactions among the three groups(P > 0. 05).Conclusion CYP2C19 gene polymorphism has a certain effect on the drug-drug interactions between clopidogrel and rabeprazole,and the combination of two drugs should be considered in the clinic.更多还原