The assessment of potential for QT interval prolongation with new pharmaceuticals: impact on drug development.
Few examinations of a single physiological variable can end the development of a putative new pharmaceutical. Prolongation of the electrocardiographic QT interval is one of these tests. Recognizing the removal of several approved and widely used medicines, worldwide regulatory authorities have raised a heightened awareness on the submission of data surrounding the ventricular repolarization process. This review will discuss the anatomy and physiology surrounding the generation of the electrocardiographic QT interval and the consequences of its alteration. In addition, relevant models of preclinical safety and general guidelines for clinical examination in this area are discussed along with the impact of incorporating these assays into the drug development process.
Gralinski
M R
MR
Safety Pharmacology Department, J-308B, Metabolism and Safety Evaluation, Pharmacia Corporation, 4901 Searle Parkway, Skokie, IL 60077, USA. michael.r.gralinski@monsanto.com
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D004562:Electrocardiography / Q000187:drug effects*; D006321:Heart / Q000502:physiology; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*