An Overview of QT Interval Assessment in Safety Pharmacology

Philippe Guillaume1, Sonia Goineau1, Guillaume Froget1

1 Porsolt SAS, Le Genest‐Saint‐Isle, France
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 10.7
DOI:  10.1002/0471141755.ph1007s61
Online Posting Date:  June, 2013
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Medicinal products that prolong cardiac repolarization, as assessed in terms of prolongation of the QT interval of the electrocardiogram, may trigger torsade de pointe, a potentially fatal arrhythmia. The lethality of this risk necessitates a detailed preclinical evaluation before initiating clinical trials. The strategy for assessing the potential of new chemical entities to cause QT interval prolongation involves two complementary approaches. An in vivo test provides information on the potential of the agent to prolong the QT interval under near‐physiological conditions. The results are mostly descriptive, providing little insight into the mechanisms of action. In vitro experiments provide more mechanistic data, although the test procedure is far removed from the clinical situation. While both approaches have reasonable predictive value, the results may depend largely on the experimental conditions employed. Discussed in this unit are experimental issues that should be considered when testing agents for their potential to cause arrhythmias, as well as general strategies for understanding the problems associated with this cardiovascular risk. Curr. Protoc. Pharmacol. 61:10.7.1‐10.7.14 © 2013 by John Wiley & Sons, Inc.

Keywords: cardiac risk assessment; drug‐induced arrhythmias; QT interval prolongation; safety pharmacology; torsades de pointes

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Table of Contents

  • Introduction
  • Cardiac Arrhythmias and QT Interval Prolongation: A Clinical Background
  • Safety Pharmacology: Critical Parameters
  • Strategic Approach for Safety Pharmacology Studies
  • General Conclusions
  • Figures
  • Tables
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