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Related Experiment Videos

Dofetilide, a novel class III antiarrhythmic agent.

H S Rasmussen1, M J Allen, K J Blackburn

  • 1Department of Clinical Research and Discovery Biology, Pfizer Central Research, Kent, England.

Journal of Cardiovascular Pharmacology
|January 1, 1992
PubMed
Summary

Dofetilide, a selective class III antiarrhythmic, effectively treats re-entrant tachyarrhythmias by prolonging cardiac refractory periods. It demonstrates a favorable safety profile and predictable pharmacokinetics in clinical studies.

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Area of Science:

  • Pharmacology
  • Cardiology
  • Electrophysiology

Background:

  • Dofetilide is a potent class III antiarrhythmic agent targeting re-entrant tachyarrhythmias.
  • Its mechanism involves selective inhibition of the rapid component of the outward potassium current (IKr).

Purpose of the Study:

  • To evaluate the efficacy and safety of dofetilide in treating various tachyarrhythmias.
  • To characterize the electrophysiological and pharmacokinetic properties of dofetilide.

Main Methods:

  • Animal studies in dogs to assess electrophysiological effects.
  • Clinical trials in healthy volunteers and patients with arrhythmias.
  • Pharmacokinetic and pharmacodynamic analyses, including QTc interval measurements.

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Main Results:

  • Dofetilide selectively inhibits IKr, prolonging action potential duration and effective refractory period.
  • Demonstrated dose-dependent prolongation of refractory periods and elevated ventricular fibrillation threshold in animals.
  • Clinical studies showed good tolerability, predictable pharmacokinetics with a 9-10h half-life, and dose-dependent QTc prolongation without impairing contractility or conduction.

Conclusions:

  • Dofetilide is a highly selective class III antiarrhythmic agent.
  • It effectively modulates myocardial repolarization and refractory periods.
  • The drug exhibits a favorable safety and pharmacokinetic profile for treating tachyarrhythmias.