Characterization of the inhibitory effects of erythromycin and clarithromycin on the HERG potassium channel.

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Stanat SJ, Carlton CG, Crumb WJ Jr, Agrawal KC, Clarkson CW

Characterization of the inhibitory effects of erythromycin and clarithromycin on the HERG potassium channel.

Mol Cell Biochem. 2003 Dec;254(1-2):1-7.

PubMed ID

14674677 [ View in PubMed

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Abstract

Both erythromycin and clarithromycin have been reported to cause QT prolongation and the cardiac arrhythmia torsade de pointes in humans, however direct evidence documenting that these drugs produce this effect by blocking human cardiac ion channels is lacking. The goal of this study was to test the hypothesis that these macrolide antibiotics significantly block the delayed rectifier current (IKr) encoded by HERG (the human ether-a-go-go-related gene) at drug concentrations, temperature and ionic conditions mimicking those occurring in human subjects. Potassium currents in HEK 293 cells stably transfected with HERG were recorded using a whole cell voltage clamp method. Exposure of cells to erythromycin reduced the HERG encoded potassium current in a concentration dependent manner with an IC50 of 38.9 +/- 1.2 microM and Hill Slope factor of 0.4 +/- 0.1. Clarithromycin produced a similar concentration-dependent block with an IC50 of 45.7 +/- 1.1 microM and Hill Slope factor of 1.0 +/- 0.1. Erythromycin (25-250 microM) and clarithromycin (5 or 25 microM) also produced a significant decrease in the integral of the current evoked by an action potential shaped voltage clamp protocol. The results of this study document that both erythromycin and clarithromycin significantly inhibit the HERG potassium current at clinically relevant concentrations.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Erythromycin	Potassium voltage-gated channel subfamily H member 2	Protein	Humans	No	Inhibitor	Details