Assessment of the effect of a single oral dose of telithromycin on sotalol-induced qt interval prolongation in healthy women

Br J Clin Pharmacol. 2005 Aug;60(2):120-7. doi: 10.1111/j.1365-2125.2005.02395.x.

Abstract

Aims: Telithromycin belongs to ketolides, a new class of macrolide antibiotics. Macrolides are known to have the potential to prolong QT interval duration. Previous studies have shown that telithromycin did not induce significant QT interval prolongation in healthy subjects compared with placebo. The main objective of this study was to demonstrate the absence of amplification of QT interval prolongation induced by sotalol, when telithromycin and sotalol were co-administered. The secondary objective was to correlate the QT interval changes induced by the study drugs to plasma concentrations during the elimination phase.

Methods: Twenty-four women received sotalol (160 mg) together with placebo or telithromycin (800 mg) in a two-period, double-blind, randomized study. Electrocardiograms were recorded at rest. Comparison of maximal corrected QT interval (QTc(max)) with sotalol in the presence or absence of telithromycin was performed. The relation between sotalol concentration and QTc was studied using linear regression.

Results: Mean difference (95% CI) between QTc(max) with sotalol-placebo and QTc(max) with sotalol-telithromycin was -15.5 ms (-27.7 to -3.2 ms). QTc(max) interval prolongation was lower (P < 0.05) with sotalol-telithromycin than with sotalol-placebo, in relation to decreased sotalol plasma concentrations. Regression analysis showed that the relationship between sotalol plasma concentration and QTc interval duration was not modified by telithromycin co-administration.

Conclusion: Our results do not support a potential synergistic effect on QT interval prolongation between sotalol and telithromycin. The decrease of mean QTc interval in subjects taking telithromycin and sotalol may be explained by a decrease of sotalol concentration.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-Arrhythmia Agents / administration & dosage*
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / pharmacokinetics
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics
  • Double-Blind Method
  • Drug Interactions
  • Electrocardiography / methods
  • Female
  • Humans
  • Ketolides / administration & dosage*
  • Ketolides / adverse effects
  • Ketolides / pharmacokinetics
  • Long QT Syndrome / chemically induced*
  • Sotalol / administration & dosage*
  • Sotalol / adverse effects
  • Sotalol / pharmacokinetics
  • Ventricular Function / drug effects*

Substances

  • Anti-Arrhythmia Agents
  • Anti-Bacterial Agents
  • Ketolides
  • Sotalol
  • telithromycin