New cell models and assays in cardiac safety profiling.
Drug-induced prolongation of the QT interval in the electrocardiogram has been associated with life-threatening ventricular tachycardia of the Torsades de Pointes type. To prevent this risk to patients, all new drug entities must undergo thorough in vitro and preclinical in vivo testing. Because a hERG channel block is the primary reason for ventricular repolarisation, disturbances causing a QT interval prolongation, established in vitro test systems focus on the analysis of drug action on hERG channel function. More sophisticated assays study ventricular repolarisation directly with cardiac tissue preparations. In addition, in the future, novel biological models, such as stem-cell-derived cardiomyocytes and cardiac tissue slices, may allow the design of innovative assay systems to address relevant cardiac safety pharmacology parameters. In this review, established as well as innovative assays and cell models used in these assays are discussed.
Meyer
Thomas
T
Multi Channel Systems MCS GmbH, Aspenhaustr. 21, 72770 Reutlingen, Germany. meyer@multichannelsystems.com
Sartipy
Peter
P
Blind
Franziska
F
Leisgen
Christine
C
Guenther
Elke
E
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D004562:Electrocardiography / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology