HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Electrophysiologic profile and efficacy of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with sustained monomorphic ventricular tachycardia. Dofetilide Arrhythmia Study Group.

Abstract
There is increasing evidence that class III antiarrhythmic agents may be superior to class I agents for the long-term treatment of life-threatening ventricular tachyarrhythmias. This open study evaluated the acute electrophysiologic effects, antiarrhythmic efficacy, and safety of different doses of intravenous dofetilide, a new class III drug, in 50 patients with sustained monomorphic ventricular tachycardia inducible by programmed electrical stimulation who had previously been unsuccessfully treated with 0 to 7 (median 3) other drugs. Intravenous dofetilide was administered over 60 minutes at the following dose levels: 1.5, 3.0, 6.0, 9.0, and 15.0 micrograms/kg. Significant class III activity was apparent at doses of 3.0 to 15.0 micrograms/kg, as evidenced by dose-related prolongation of the QTc interval by 13.4% to 14.2%, ventricular effective refractory period by 7.9% to 20.6%, and ventricular functional refractory period by 7.3% to 25.0%. The corresponding mean +/- SD plasma dofetilide concentrations ranged from 1.45 +/- 0.52 to 6.48 +/- 1.31 ng/ml. There was no evidence of reverse use-dependence. At these electrophysiologically active dose levels, intravenous dofetilide suppressed (complete response) or slowed (partial response) inducible ventricular tachycardia in 17 of 41 patients (41%) compared with 0 of 9 patients receiving only 1.5 micrograms/kg. The response rate was fairly uniform among the groups receiving 3.0, 6.0, 9.0, and 15.0 micrograms/kg. Intravenous dofetilide was hemodynamically well tolerated. Torsades de pointes (which was self-limiting) developed in only 1 patient, who was allocated to receive 15.0 micrograms/kg. There were no other proarrhythmic episodes or serious adverse effects. Further evaluation of the therapeutic potential of dofetilide in the management of life-threatening ventricular arrhythmias is justified.
AuthorsY Bashir, P E Thomsen, J H Kingma, M Møller, C Wong, S M Cobbe, L Jordaens, R W Campbell, H S Rasmussen, A J Camm
JournalThe American journal of cardiology (Am J Cardiol) Vol. 76 Issue 14 Pg. 1040-4 (Nov 15 1995) ISSN: 0002-9149 [Print] United States
PMID7484858 (Publication Type: Case Reports, Clinical Trial, Controlled Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Arrhythmia Agents
  • Phenethylamines
  • Sulfonamides
  • dofetilide
Topics
  • Aged
  • Anti-Arrhythmia Agents (administration & dosage, therapeutic use)
  • Electric Stimulation
  • Electrophysiology
  • Europe
  • Female
  • Hemodynamics (drug effects)
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Phenethylamines (administration & dosage, therapeutic use)
  • Sulfonamides (administration & dosage, therapeutic use)
  • Tachycardia, Ventricular (drug therapy, physiopathology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: