Cardiac safety assays.
Cardiac safety, including the risk of drug-induced 'torsades de pointes' (TdP) arrhythmia, is a major concern in the development, approval and prescription of new drugs. Assessment of surrogate markers of TdP-risk, such as QT-interval prolongation or inhibition of the rapid delayed-rectifier K(+)-current (IKr) encoded by the human ether-a-go-go-related gene (hERG), is therefore required before drug approval. Here, we review some methodologies employed to assess proarrhythmia liability of drugs, discuss the challenges involved in this process, and highlight promising novel cardiac-safety assays.
Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany.
Jordi
J
Heijman
Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany.
Niels
N
Voigt
AstraZeneca Research & Development, Bioscience, Mölndal, Sweden.
Leif G
LG
Carlsson
Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany. Electronic address: Dobromir.Dobrev@uk-essen.de.
Dobromir
D
Dobrev
D000818:Animals; D051668:Delayed Rectifier Potassium Channels / Q000037:antagonists & inhibitors; D064420:Drug-Related Side Effects and Adverse Reactions; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000517:prevention & control*
D051668:Delayed Rectifier Potassium Channels