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A dose‐ranging study of UK‐68,798, a novel class III anti‐arrhythmic agent, in normal volunteers.
Author(s) -
Gemmill JD,
Howie CA,
Meredith PA,
Kelman AW,
Rasmussen HS,
Hillis WS,
Elliott HL
Publication year - 1991
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1991.tb03926.x
Subject(s) - dose ranging study , medicine , qt interval , placebo , pharmacokinetics , pharmacology , antiarrhythmic agent , volume of distribution , anesthesia , cardiology , double blind , heart disease , pathology , alternative medicine
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.