Drug-induced QT prolongation: Concordance of preclinical anesthetized canine model in relation to published clinical observations for ten CiPA drugs


Journal of Pharmacological and Toxicological Methods


Yevgeniya E. Koshman, Amanda S.Wilsey Brandan M.Bird Aimee L. Endemann Sabine Sadilek, Jessica Treadway, Ruth L. Martin, James S. Polakowski, Gary A.Gintant, Scott W.Mittelstadt



The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative differentiates torsadogenic risk of 28 drugs affecting ventricular repolarization based on multiple in vitro human-derived ionic currents. However, a standardized prospective assessment of the electrophysiologic effects of these drugs in an integrated in vivo preclinical cardiovascular model is lacking. This study questioned whether QTc interval prolongation in a preclinical in vivo model could detect clinically reported QTc prolongation and assign torsadogenic risk for ten CiPA drugs.

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