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Comparative Study of the Effects of Erythromycin and Roxithromycin on Action Potential Duration and Potassium
1Department of Clinical Pharmacology, St. Vincent's Hospital, Sydney, Australia
Abstract:
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.
Insights
Erythromycin prolongs cardiac action potential, unlike roxithromycin. While both macrolide antibiotics block potassium currents, roxithromycin poses a remote risk of proarrhythmia in clinical use.
Area of Science:
- Pharmacology
- Cardiovascular Electrophysiology
Background:
- Erythromycin and roxithromycin are common macrolide antibiotics.
- Erythromycin can cause dangerous cardiac arrhythmias (torsades de pointes) by blocking potassium currents essential for heart rhythm.
- Understanding the comparative cardiac effects of these drugs is crucial for patient safety.
Purpose of the Study:
- To compare the effects of erythromycin and roxithromycin on cardiac action potential duration and potassium currents.
- To assess the relative risk of proarrhythmia associated with these two macrolide antibiotics.
Main Methods:
- Utilized standard cellular electrophysiology and whole-cell patch-clamping techniques.
- Tested drug effects on canine Purkinje fibers and isolated rabbit ventricular myocytes.
- Measured action potential duration and blockade of specific potassium currents.
Main Results:
- Erythromycin significantly prolonged action potential duration in canine Purkinje fibers at 100 µM; roxithromycin did not.
- Both erythromycin and roxithromycin significantly depressed the delayed rectifier potassium current in rabbit ventricular myocytes at concentrations of ≥30 µM.
- The drugs exhibited similar potencies in blocking the delayed rectifier current.
Conclusions:
- Erythromycin, but not roxithromycin, prolonged cardiac action potential duration.
- Both drugs inhibit key potassium currents, but roxithromycin's risk of causing proarrhythmia during typical oral use is very low.
- Clinical risk assessment favors roxithromycin over erythromycin regarding proarrhythmic potential.