Predicting QT prolongation in humans during early drug development using hERG inhibition and an anaesthetized guinea-pig model.

ABSTRACT:

Background and purpose

Drug-induced prolongation of the QT interval can lead to torsade de pointes, a life-threatening ventricular arrhythmia. Finding appropriate assays from among the plethora of options available to predict reliably this serious adverse effect in humans remains a challenging issue for the discovery and development of drugs. The purpose of the present study was to develop and verify a reliable and relatively simple approach for assessing, during preclinical development, the propensity of drugs to prolong the QT interval in humans.

Experimental approach

Sixteen marketed drugs from various pharmacological classes with a known incidence -- or lack thereof -- of QT prolongation in humans were examined in hERG (human ether a-go-go-related gene) patch-clamp assay

SUBMITTER: Yao X 

PROVIDER: S-EPMC2442905 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature