An overview of QT interval assessment in safety pharmacology.

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. © 2013 by John Wiley & Sons, Inc.

Citation

Philippe Guillaume, Sonia Goineau, Guillaume Froget. An overview of QT interval assessment in safety pharmacology. Current protocols in pharmacology / editorial board, S.J. Enna (editor-in-chief) ... [et al.]. 2013 Jun;Chapter 10:Unit 10.7

PMID: 23744709

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