Pharmacokinetics and metabolism of dofetilide in mouse, rat, dog and man

Xenobiotica. 1992 Jun;22(6):709-19. doi: 10.3109/00498259209053133.


1. Pharmacokinetics of dofetilide were studied in man, dog, rat and mouse after single i.v. and oral doses of dofetilide or 14C-dofetilide. 2. Dofetilide was absorbed completely in all species. Low metabolic clearance in man resulted in complete bioavailability following oral administration. Higher metabolic clearance in rodents, and to a lesser extent dogs, resulted in decreased bioavailability because of first-pass metabolism. 3. Following i.v. administration, the volume of distribution showed only moderate variation in all species (2.8-6.3 l/kg). High plasma clearance in rodents resulted in short half-life values (mouse 0.32, male rat 0.5 and female rat 1.2 h), whilst lower clearance in dog and man gave longer terminal elimination half-lives (4.6 and 7.6 h respectively). 4. After single i.v. doses of 14C-dofetilide, unchanged drug was the major component excreted in urine of all species with several metabolites also present. 5. Metabolites identified in urine from all species were formed by N-oxidation or N-dealkylation of the tertiary nitrogen atom of dofetilide. 6. After oral and i.v. administration of 14C-dofetilide to man, parent compound was the only detectable component present in plasma and represented 75% of plasma radioactivity. No single metabolite accounted for greater than 5% of plasma radioactivity.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Arrhythmia Agents / blood
  • Anti-Arrhythmia Agents / pharmacokinetics*
  • Anti-Arrhythmia Agents / urine
  • Dogs
  • Female
  • Humans
  • Infusions, Intravenous
  • Injections, Intravenous
  • Male
  • Mice
  • Phenethylamines / blood
  • Phenethylamines / pharmacokinetics*
  • Phenethylamines / urine
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonamides / blood
  • Sulfonamides / pharmacokinetics*
  • Sulfonamides / urine


  • Anti-Arrhythmia Agents
  • Phenethylamines
  • Sulfonamides
  • dofetilide