药物诱导的心律失常非临床体外评价研究进展

潘东升, 王三龙, 张颖丽, 陈思蓉, 李波

中国药学杂志 ›› 2020, Vol. 55 ›› Issue (13) : 1053-1059.

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中国药学杂志 ›› 2020, Vol. 55 ›› Issue (13) : 1053-1059. DOI: 10.11669/cpj.2020.13.001
综述

药物诱导的心律失常非临床体外评价研究进展

  • 潘东升, 王三龙, 张颖丽, 陈思蓉, 李波*
作者信息 +

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

  • PAN Dong-sheng, WANG San-long, ZHANG Ying-li, CHEN Si-rong, LI Bo*
Author information +
文章历史 +

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1 479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。

Abstract

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, 1 479 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

Key words

drug-induced arrhythmia / torsade de pointes / human induced pluripotent stem cell-derived cardiomyocytes / action potential / field potential / hERG blocking

引用本文

导出引用
潘东升, 王三龙, 张颖丽, 陈思蓉, 李波. 药物诱导的心律失常非临床体外评价研究进展[J]. 中国药学杂志, 2020, 55(13): 1053-1059 https://doi.org/10.11669/cpj.2020.13.001
PAN Dong-sheng, WANG San-long, ZHANG Ying-li, CHEN Si-rong, LI Bo. Research Advances on Non-Clinical Evaluation in Vitro of Drug-Induced Arrhythmias[J]. Chinese Pharmaceutical Journal, 2020, 55(13): 1053-1059 https://doi.org/10.11669/cpj.2020.13.001
中图分类号: R965   

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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)
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