An Overview of QT Interval Assessment in Safety Pharmacology

Medicinal products that prolong cardiac repolarization unintentionally, as assessed in terms of prolongation of the QT interval of the electrocardiogram, may trigger a potentially fatal arrhythmia called torsade de pointe (TDP). This lethal risk necessitates a robust preclinical evaluation before engaging in clinical trials. There are two different and complementary approaches to assess the potential of drugs to cause QT interval prolongation. The in vivo approach provides information on the potential of the compound to prolong the QT interval under near‐physiological conditions. It is mostly descriptive and not explanatory in terms of mechanisms of action. The in vitro approach provides much more mechanistic information, but is far removed from the clinical situation. Both approaches appear to possess reasonable predictive value, but the results obtained may largely depend on the experimental conditions used. This unit describes and presents an analytic strategy aimed at understanding the problems associated with this cardiovascular risk.