Meyer Thomas, Sartipy Peter, Blind Franziska, Leisgen Christine, Guenther Elke
Multi Channel Systems MCS GmbH, Aspenhaustr. 21, 72770 Reutlingen, Germany.
Expert Opin Drug Metab Toxicol. 2007 Aug;3(4):507-17. doi: 10.1517/17425225.3.4.507.
Drug-induced prolongation of the QT interval in the electrocardiogram has been associated with life-threatening ventricular tachycardia of the Torsades de Pointes type. To prevent this risk to patients, all new drug entities must undergo thorough in vitro and preclinical in vivo testing. Because a hERG channel block is the primary reason for ventricular repolarisation, disturbances causing a QT interval prolongation, established in vitro test systems focus on the analysis of drug action on hERG channel function. More sophisticated assays study ventricular repolarisation directly with cardiac tissue preparations. In addition, in the future, novel biological models, such as stem-cell-derived cardiomyocytes and cardiac tissue slices, may allow the design of innovative assay systems to address relevant cardiac safety pharmacology parameters. In this review, established as well as innovative assays and cell models used in these assays are discussed.
药物诱导的心电图QT间期延长与危及生命的尖端扭转型室性心动过速有关。为防止给患者带来这种风险，所有新的药物实体都必须经过全面的体外和临床前体内测试。由于人ether-à-go-go相关基因（hERG）通道阻滞是心室复极的主要原因，而QT间期延长正是由这种干扰引起的，因此现有的体外测试系统主要侧重于分析药物对hERG通道功能的作用。更复杂的检测方法则直接利用心脏组织制剂研究心室复极。此外，未来新型生物模型（如干细胞衍生的心肌细胞和心脏组织切片）可能会促使设计出创新的检测系统，以解决相关的心脏安全药理学参数问题。在这篇综述中，将讨论现有的以及创新的检测方法和这些检测方法中使用的细胞模型。
