期刊
EXPERT REVIEW OF CARDIOVASCULAR THERAPY
卷 14, 期 2, 页码 245-253出版社
TAYLOR & FRANCIS INC
DOI: 10.1586/14779072.2016.1116940
关键词
Cardiac arrhythmias; drugs; electrophysiology; cardiac safety; animal models
资金
- University Medical Center, Utrecht, the Netherlands
Drug-induced Torsade de Pointes arrhythmia is a life-threatening adverse effect feared by pharmaceutical companies. For the last decade, the cardiac safety guidelines have imposed human ether-a-go-go-related gene channel blockade and prolongation of QT interval as surrogates for proarrhythmic risk propensity of a new chemical entity. Suffering from a lack of specificity, this assessment strategy led to a great amount of false positive outcomes. Therefore, this review will discuss new pharmaceutical strategies: the cardiac safety proposal that recently emerged, the Comprehensive in vitro Proarrhythmia Assay, combining in vitro assays that integrate effects on main cardiac ion channels, with computational models of human ventricular action potential as well as assays using human stem cell-derived cardiomyocytes for an improved prediction of drug's proarrhythmic liability, alternative pharmacological perspectives as well as the current treatment of drug-induced long QT syndrome.
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