UNIT 10.16 Predicting Drug-Induced QT Prolongation and Torsades de Pointes: A Review of Preclinical Endpoint Measures

  1. Claire Townsend1,
  2. Barry S. Brown2

Published Online: 1 JUN 2013

DOI: 10.1002/0471141755.ph1016s61

Current Protocols in Pharmacology

Current Protocols in Pharmacology

How to Cite

Townsend, C. and Brown, B. S. 2013. Predicting Drug-Induced QT Prolongation and Torsades de Pointes: A Review of Preclinical Endpoint Measures. Current Protocols in Pharmacology. 61:10.16:10.16.1–10.16.19.

Author Information

  1. 1

    GlaxoSmithKline Biological Reagents and Assay Development, Research Triangle Park, North Carolina

  2. 2

    GlaxoSmithKline Safety Pharmacology, King of Prussia, Pennsylvania

Publication History

  1. Published Online: 1 JUN 2013


Compound-induced prolongation of the cardiac QT interval is a major concern in drug development and this unit discusses approaches that can predict QT effects prior to undertaking clinical trials. The majority of compounds that prolong the QT interval block the cardiac rapid delayed rectifier potassium current, IKr (hERG). Described in this overview are different ways to measure hERG, from recent advances in automated electrophysiology to the quantification of channel protein trafficking and binding. The contribution of other cardiac ion channels to hERG data interpretation is also discussed. In addition, endpoint measures of the integrated activity of cardiac ion channels at the single-cell, tissue, and whole-animal level, including for example the well-established action potential to the more recent beat-to-beat variability, transmural dispersion of repolarization, and field potential duration, are described in the context of their ability to predict QT prolongation and torsadogenicity in humans. Curr. Protoc. Pharmacol. 61:10.16.1-10.16.19 © 2013 by John Wiley & Sons, Inc.


  • cardiac ion channels;
  • QT prolongation;
  • hERG;
  • drug discovery;
  • safety