Key result
Erythromycin, but not roxithromycin, significantly prolonged action potential duration at 100 µM, though both reduced the delayed rectifier potassium current (50% vs 36% reduction at 100 µM).
Why the study?
Does roxithromycin have a different effect on action potential duration and potassium currents compared to erythromycin in canine and rabbit cardiac models?
Does roxithromycin have a different effect on action potential duration and potassium currents compared to erythromycin in canine and rabbit cardiac models?
Absolute Event Rate: 50% vs 36%
Roxithromycin does not significantly prolong action potential duration at high concentrations unlike erythromycin, suggesting a lower proarrhythmic risk during normal clinical use.
Roxithromycin may carry lower proarrhythmic risk than erythromycin in animal models; leaves open translation to clinical outcomes.
BACKGROUND: Erythromycin and roxithromycin are macrolide antibiotics in common clinical use. Erythromycin occasionally produces life-threatening arrhythmias (torsades de pointes) by blocking the outward potassium current responsible for repolarization of the cardiac action potential. METHODS AND RESULTS: We used standard cellular electrophysiological and whole-cell patch-clamping techniques to compare the relative efficacy of erythromycin and roxithromycin in prolonging cardiac action potential in canine Purkinje fibers and in blocking individual outward potassium currents in isolated rabbit ventricular myocytes. We demonstrated significant prolongation of action potential duration in canine Purkinje fibers by erythromycin but not roxithromycin at a concentration of 100 µM. The delayed rectifier, the outward potassium current thought to be most sensitive to modulation by drugs, was significantly depressed by both agents at concentrations of >/=30 µM in isolated rabbit ventricular myocytes. Both drugs had similar potencies (26% and 21% reduction by 30 µM erythromycin and roxithromycin, respectively, and 50% and 36% reduction by 100 µM erythromycin and roxithromycin). Neither agent significantly blocked other potassium currents (including the transient outward current). CONCLUSIONS: Taking into account normally observed peak blood concentrations of these agents in clinical use and the fact that roxithromycin is not normally administered intravenously, we conclude that the risk of proarrhythmia during normal clinical use of oral roxithromycin is extremely remote.
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West et al. (1998) studied this question. Erythromycin vs. Roxithromycin was evaluated on Reduction of the delayed rectifier outward potassium current at 100 µM. Erythromycin, but not roxithromycin, significantly prolonged action potential duration at 100 µM, though both reduced the delayed rectifier potassium current (50% vs 36% reduction at 100 µM).
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