ABSTRACT
The QT interval is measured from the beginning of Q wave to the end of T wave on an electrocardiagram (ECG) tracing (see Figure 4.1). It reflects the duration of ventricular depolarization and subsequent repolarization. For some drugs, significant prolongation of the absolute QT interval has been associated with the precipitation of a potentially fatal cardiac arrhythmia called torsades de pointes (TdP) and can degenerate into ventricular fibrillation, leading to sudden cardiac death (Moss, 1993). Over the past one and half decades, these cardiac adverse events have resulted in a number of patient deaths and were one of the most frequent adverse events (Wysowski et al., 2001) of a drug that led to either its removal from themarket (e.g., terfenadine and cisapride) or the placement of restrictions on its use (e.g., ziprasidone and ranolizine.) With theses experiences, the regulatory agencies now request that each pharmaceutical company conduct at least one thorough QT (TQT) study when submitting an application of any new nonantiarrhythmic drug. The ICH E14 guidance for The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Nonantiarrhythmic Drugs was released in May 2005. The abbreviation QTc denotes the QT interval corrected for the heart rate (HR).
