Literature DB >> 1958435

A dose-ranging study of UK-68,798, a novel class III anti-arrhythmic agent, in normal volunteers.

J D Gemmill1, C A Howie, P A Meredith, A W Kelman, H S Rasmussen, W S Hillis, H L Elliott.   

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.

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Year:  1991        PMID: 1958435      PMCID: PMC1368601          DOI: 10.1111/j.1365-2125.1991.tb03926.x

Source DB:  PubMed          Journal:  Br J Clin Pharmacol        ISSN: 0306-5251            Impact factor:   4.335


  8 in total

1.  Measurement of the class III antidysrhythmic drug, UK-68,798, in plasma by radioimmunoassay.

Authors:  D K Walker; G W Aherne; J E Arrowsmith; P E Cross; B Kaye; D A Smith; D A Stopher; W Wild
Journal:  J Pharm Biomed Anal       Date:  1991       Impact factor: 3.935

2.  Measurement of the QT interval.

Authors:  R W Campbell; P Gardiner; P A Amos; D Chadwick; R S Jordan
Journal:  Eur Heart J       Date:  1985-11       Impact factor: 29.983

3.  Quantitative analysis of the disopyramide concentration-effect relationship.

Authors:  B Whiting; N H Holford; L B Sheiner
Journal:  Br J Clin Pharmacol       Date:  1980-01       Impact factor: 4.335

Review 4.  Clinical pharmacokinetics of the newer antiarrhythmic agents.

Authors:  A M Gillis; R E Kates
Journal:  Clin Pharmacokinet       Date:  1984 Sep-Oct       Impact factor: 6.447

5.  Pharmacokinetic significance of serum reverse T3 levels during amiodarone treatment: a potential method for monitoring chronic drug therapy.

Authors:  K Nademanee; B N Singh; J A Hendrickson; A W Reed; S Melmed; J Hershman
Journal:  Circulation       Date:  1982-07       Impact factor: 29.690

6.  Delayed ventricular repolarization as an anti-arrhythmic principle.

Authors:  E M Vaughan Williams
Journal:  Eur Heart J       Date:  1985-11       Impact factor: 29.983

7.  The QT interval: a predictor of the plasma and myocardial concentrations of amiodarone.

Authors:  N M Debbas; C du Cailar; R S Bexton; J G Demaille; A J Camm; P Puech
Journal:  Br Heart J       Date:  1984-03

Review 8.  Load induction of cardiac hypertrophy.

Authors:  G Cooper; R L Kent; D L Mann
Journal:  J Mol Cell Cardiol       Date:  1989-12       Impact factor: 5.000

  8 in total
  4 in total

1.  Pharmacodynamic effect of continuous vs intermittent dosing of dofetilide on QT interval.

Authors:  Michael J Allen; Stuart D Oliver; Margaret W Newgreen; Donald J Nichols
Journal:  Br J Clin Pharmacol       Date:  2002-01       Impact factor: 4.335

Review 2.  Dofetilide: a review of its use in atrial fibrillation and atrial flutter.

Authors:  K J McClellan; A Markham
Journal:  Drugs       Date:  1999-12       Impact factor: 9.546

3.  The use of clinical irrelevance criteria in covariate model building with application to dofetilide pharmacokinetic data.

Authors:  Karin Tunblad; Lars Lindbom; Lynn McFadyen; E Niclas Jonsson; Scott Marshall; Mats O Karlsson
Journal:  J Pharmacokinet Pharmacodyn       Date:  2008-11-15       Impact factor: 2.745

4.  Effects of altered extracellular potassium and pacing cycle length on the class III antiarrhythmic actions of dofetilide (UK-68,798) in guinea-pig papillary muscle.

Authors:  T Yang; P M Tande; D A Lathrop; H Refsum
Journal:  Cardiovasc Drugs Ther       Date:  1992-08       Impact factor: 3.727

  4 in total

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