QT interval prolongation by noncardiovascular drugs: issues and solutions for novel drug development

In 1997, the Committee for Proprietary Medicinal Products (CPMP) issued a d ocument concerning the potential of non-cardiovascular drugs to cause prolo ngation of the QT interval of the electrocardiogram. This article reviews s everal aspects of this complex problem, including a preclinical strategy (i n vitro electrophysiology in human cardiac cells and in vivo pharmacologica lly validated conscious dogs) to satisfy the expectations of the CPMP. In p articular, the discussion stresses the danger of drugs prolonging the QT in terval in patients with concurrent cardiac risk factors and the need for ri gorous clinical testing to determine the risk of fatal cardiac events for d rugs with the propensity to prolong QT.