title: Electropharmacologic effects and pharmacokinetics of almokalant, a new class III antiarrhythmic, in patients with healed or healing myocardial infarcts and complex ventricular arrhythmias.
abstract: The electropharmacologic effects and pharmacokinetics of almokalant, a new class III antiarrhythmic, were investigated in a randomized, placebo-controlled, double-blind study, and efficacy was evaluated. Ten post-myocardial infarction patients with complex ventricular arrhythmias were included and received, in randomized order on consecutive days, 4.5 mg (12.8 mumol) of almokalant or placebo intravenously over 10 minutes. One patient received infusion at a higher rate and developed self-terminating torsades de pointes. In the remaining 9 patients the corrected QT interval increased significantly: At the end of placebo infusion the corrected QT was 445 +/- 18 ms and after almokalant 548 +/- 53 ms (p = 0.0015). The signal-averaged electrocardiographic parameters did not change. The number of ventricular premature complexes decreased significantly during the first 15 minutes after almokalant infusion (p = 0.04). No additional proarrhythmic or other significant adverse events were noted. The almokalant plasma concentration showed a biphasic decrease with an elimination half-life of 2.4 +/- 0.1 hours. Almokalant was rapidly cleared from the body with a clearance of 11 +/- 1 ml/min/kg. When given with certain precautions almokalant appears safe and well-tolerated and may be antiarrhythmic by prolonging refractoriness.
authors.affiliation: Department of Cardiology, University Hospital Groningen, The Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: Wiesfeld
authors.forename: H J
authors.initials: HJ
authors.lastname: Crijns
authors.forename: T J
authors.initials: TJ
authors.lastname: Tobé
authors.forename: O
authors.initials: O
authors.lastname: Almgren
authors.forename: R H
authors.initials: RH
authors.lastname: Bergstrand
authors.forename: J
authors.initials: J
authors.lastname: Aberg
authors.forename: J
authors.initials: J
authors.lastname: Haaksma
authors.forename: K I
authors.initials: KI
authors.lastname: Lie
mesh_terms: D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005117:Cardiac Complexes, Premature / Q000503:physiopathology*; D004311:Double-Blind Method; D004562:Electrocardiography / Q000379:methods; D015716:Electrocardiography, Ambulatory; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000503:physiopathology*; D011412:Propanolamines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D012815:Signal Processing, Computer-Assisted
chemical_list: D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; C074334:almokalant