A DOSE-RANGING STUDY OF UK-68,798, A NOVEL CLASS-III ANTIARRHYTHMIC AGENT, IN NORMAL VOLUNTEERS

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-mu-g 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 antiarrhythmic activity and merits further assessment in clinical studies.