Moving towards better predictors of drug-induced torsades de pointes.
Drug-induced torsades de pointes (TdP) remains a significant public health concern that has challenged scientists who have the responsibility of advancing new medicines through development to the patient, while assuring public safety. As a result, from the point of discovering a new molecule to the time of its registration, significant efforts are made to recognize potential liabilities, including the potential for TdP. With this background, the ILSI (HESI) Proarrhythmia Models Project Committee recognized that there was little practical understanding of the relationship between drug effects on cardiac ventricular repolarization and the rare clinical event of TdP. A workshop was therefore convened at which four topics were considered including: Molecular and Cellular Biology Underlying TdP, Dynamics of Periodicity, Models of TdP Proarrhythmia and Key Considerations for Demonstrating Utility of Pre-Clinical Models. The series of publications in this special edition has established the background, areas of debate and those that deserve scientific pursuit. This is intented to encourage the research community to contribute to these important areas of investigation in advancing the science and our understanding of drug-induced proarrhythmia.
Drug Safety and Metabolism, Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA. alan.bass@spcorp.com
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D000818:Animals; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography; D006801:Humans; D018570:Risk Assessment / Q000379:methods; D016171:Torsades de Pointes / Q000139:chemically induced*