CES1基因多态性影响达比加群酯血药浓度及有效性与安全性的研究  

Research of Influence of CES1 Gene Polymorphism on Blood Concentration,Efficacy and Safety of Dabigatran Etexilate

作　　者：李菁冉 阎雨 LI Jing-ran;YAN Yu(School of administration and policy,Renmin University of China,Beijing 100872,China;Pfizer Investment Co.,Ltd.,Shanghai 200041,China;Department of Pharmacy,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]中国人民大学公共管理学院,北京100872 [2]辉瑞投资有限公司,上海200041 [3]北京中日友好医院药学部,北京100029

出　　处：《海峡药学》2023年第1期64-69,共6页Strait Pharmaceutical Journal

摘　　要：目的评估CES1基因多态性与口服达比加群酯后达比加群血药浓度及有效性、安全性的相关性,为临床提供循证依据,促进药物合理使用与上市后风险管理。方法系统检索PubMed、Embase、Cochrane Library、中国知网(CNKI)、万方和中国生物医学文献(CBM)数据库,检索日期截自建库至2022年7月9日。按纳入、排除标准筛选文献,提取资料。结果共纳入9项研究,其中7项研究对象为长期服用达比加群酯患者(2560例患者),2项为单剂量生物等效性临床研究(188名健康志愿者)。结论中国人群CES1 rs2244613和rs8192935等位基因频率与欧洲人群均有较大差异。CES1 rs2244613次要等位基因携带者(AC或CC型)相比非携带者(AA型),达比加群血药浓度降低,C/D值降低,出血风险显著降低;CES1 rs8192935次要等位基因携带者(CT或TT型)相比非携带者(CC型)达比加群血药浓度降低。CES1基因多态性与达比加群酯疗效无显著相关性。OBJECTIVE Evaluate the correlation between CES1 gene polymorphism and blood concentration,efficacy and safety of dabigatran etexilate,to provide evidence-based basis for clinical practice.METHODS The databases of PubMed,Embase,Cochrane Library,China National Knowledge Infrastructure(CNKI),WanFang and China Biomedical Literature(CBM)databases were searched from the inceptions up to July 9,2022.Articles were screened and data extracted according to the inclusion and exclusion criteria.RESULTS 9 studies were retrieved,including 7 studies involved long-term use of dabigatran etexilate(2560 patients)and 2 single-dose bioequivalence clinical trials(188 healthy volunteers).CONCLUSION The genotype frequencies of CES1 rs2244613 and CES1 rs8192935 were significantly different between Chinese and European.For the CES1 polymorphism rs2244613,the minor allele(C)carriers had lower blood concentration,C/D value and bleeding risk of dabigatran than non-carriers.For CES1 rs8192935,the minor allele(T)carriers had lower blood concentration of dabigatran than non-carriers.No significant association was observed between CES1 polymorphism and ischemic events.

关 键 词：达比加群酯 羧酸酯酶1 基因多态性 血药浓度 有效性 安全性 

分 类 号：R969.1[医药卫生—药理学]