title: A dose-ranging study of UK-68,798, a novel class III anti-arrhythmic agent, in normal volunteers.
abstract: 1. UK-68,798, a novel class III anti-arrhythmic agent was administered intravenously to twelve healthy volunteers in a placebo controlled, double-blind, dose-escalating study. 2. Doses of 5 and 10 micrograms kg-1 of UK-68,798 selectively and significantly prolonged the QT interval, with mean maximum changes of 35 and 107 ms respectively, without affecting other ECG intervals. 3. There were dose-related increases in AUC but clearance (23 l h-1), terminal elimination half-life (8 h) and volume of distribution (245 l) were found to be independent of dose with low levels of intra- and inter-patient variability. 4. UK-68,798 has electrophysiological effects indicative of selective class III anti-arrhythmic activity and merits further assessment in clinical studies.
authors.affiliation: University Department of Medicine and Therapeutics, Stobhill General Hospital, Glasgow, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Gemmill
authors.forename: C A
authors.initials: CA
authors.lastname: Howie
authors.forename: P A
authors.initials: PA
authors.lastname: Meredith
authors.forename: A W
authors.initials: AW
authors.lastname: Kelman
authors.forename: H S
authors.initials: HS
authors.lastname: Rasmussen
authors.forename: W S
authors.initials: WS
authors.lastname: Hillis
authors.forename: H L
authors.initials: HL
authors.lastname: Elliott
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D010627:Phenethylamines / Q000493:pharmacokinetics / Q000494:pharmacology*; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide