Key result
Among 576 compounds, the hERG assay alone did not adequately identify drugs inducing QT prolongation and missed drug-induced QT shortening, which can elicit ventricular fibrillation.
Population
HEK293 cells stably transfected with hERG channels; isolated Purkinje fibres and perfused hearts from rabbits
Design
Preclinical
Authors
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May warrant caution with hERG-only screening in drug development; leaves open need for broader preclinical arrhythmia assays.
The standard hERG assay is insufficient for predicting all drug-induced arrhythmias, highlighting a critical gap in regulatory guidelines regarding QT-shortening compounds.
Lu et al. (2008) studied Drug-induced QT interval changes and arrhythmias (n=576). Pharmacological compounds was evaluated on hERG current inhibition and action potential duration (APD) changes. Among 576 compounds, the hERG assay alone did not adequately identify drugs inducing QT prolongation and missed drug-induced QT shortening, which can elicit ventricular fibrillation.
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