The impact of drug-induced QT interval prolongation on drug discovery and development
Top Cited Papers
- 1 June 2003
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Drug Discovery
- Vol. 2 (6), 439-447
- https://doi.org/10.1038/nrd1108
Abstract
During the past decade, a number of non-cardiovascular drugs have had their label revised or have been withdrawn from the market because of unexpected post-marketing reports of sudden cardiac death associated with a prolongation of the QT interval, and an increased propensity to develop a ventricular tachyarrhythmia called Torsades de Pointes. Although a direct link between QT interval prolongation and arrhythmogenesis is still unclear, QT prolongation is now the subject of increased regulatory review and is considered a significant risk factor for predicting human safety of New Chemical Entities. Consequently, pharmaceutical companies are striving to improve the drug discovery and development process to identify, as early as possible, the risk of novel agents, or their metabolites, of causing QT interval prolongation and to make appropriate go/no-go decisions or modify their development programme accordingly.Keywords
This publication has 23 references indexed in Scilit:
- Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug developmentCardiovascular Research, 2003
- High Throughput Ion-Channel Pharmacology: Planar-Array-Based Voltage ClampASSAY and Drug Development Technologies, 2003
- Cardiac Ion ChannelsAnnual Review of Physiology, 2002
- Cell-based assays and instrumentation for screening ion-channel targetsDrug Discovery Today, 1999
- Pharmacokinetic and pharmacodynamic effects of high-dose continuous intravenous verapamil infusionCritical Care Medicine, 1999
- CorrespondenceInternational Journal of Cardiology, 1998
- Risks of non-sedating antihistaminesThe Lancet, 1997
- Unwitting Exposure to RiskCardiology in Review, 1993
- Verapamil-induced polymorphous ventricular tachycardiaJournal of the American College of Cardiology, 1985
- Torsade de pointes due to quinidine: Observations in 31 patientsAmerican Heart Journal, 1984