药物诱导的心律失常非临床体外评价研究进展  

Research Advances on Non-Clinical Evaluation in Vitro of Drug-Induced Arrhythmias

作　　者：潘东升[1] 王三龙[1] 张颖丽[1] 陈思蓉 李波[1] PAN Dong-sheng;WANG San-long;ZHANG Ying-li;CHEN Si-rong;LI Bo(Beijing Key Laboratory for Safety Evaluation of Drugs,National Center for Safety Evaluation of Drugs,National Institutes for Food and Drug Control,Beijing 100176,China)

机构地区：[1]中国食品药品检定研究院国家药物安全评价监测中心,药物非临床安全评价研究北京市重点实验室,北京100176

出　　处：《中国药学杂志》2020年第13期1053-1059,共7页Chinese Pharmaceutical Journal

基　　金：创新药物非临床安全性评价关键技术研究项目资助(2018ZX09201017-001)。

摘　　要：药物诱导的心律失常是导致药物研发失败的主要原因之一,也是导致药物撤市的主要原因,因此在非临床研究中准确地预测药物诱导的心律失常是降低研发失败和临床不良反应的最佳方法。笔者以“drug-induced arrhythmia”,“torsade de pointes”,“human induced pluripotent stem cell-derived cardiomyocytes”等为关键词在PUBMED、METSTR、CNKI和百度学术数据库中检索到1479篇文献,筛选后63篇符合要求;通过对文献的整理和数据分析,笔者总结了药物诱导心律失常体外评价模型的优缺点以及体外评价方法对不同类型化合物的敏感性和特异性,以期为毒性研究提供参考。Drug-induced arrhythmia is one of the main causes of failure in drug development,and it is also a major cause of drug withdrawal,therefore,accurate prediction of drug-induced arrhythmia in the non-clinical research stage is the best way to reduce cost.Literature was retrieved by formally searching PubMed,Metstr,CNKI and Baidu Scholar,1479 published articles were found through search method,63 full-text articles were included.After reviewed the relevant literatures,the advantages and disadvantages of the different experimental cells and the related evaluation methods are assessed,in order to provide reference for toxicity evaluation.

关 键 词：药物诱导的心律失常 尖端扭转型室性心律失常 人诱导多能干细胞分化的心肌细胞 动作电位 场电位 hERG通道阻滞 

分 类 号：R965[医药卫生—药理学]