1991
DOI: 10.1111/j.1365-2125.1991.tb05572.x
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Pharmacokinetic and pharmacodynamic effects of UK‐68,798, a new potential class III antiarrhythmic drug.

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Cited by 43 publications
(26 citation statements)
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“…Our previous study [2] has also indicated that at a concentration of 10 nM, dofetilide has no rate-dependent effect (reverse use-dependence), which is further confirmed by the present study. This concentration of dofetilide is within peak plasma concentrations, which are in the range of 1.74-5.11 ng/ml (i.e., 3.9-11.6 nM) following a loading infusion [14]. At high doses of dofetilide, a slight decrease or reversal of its class III effects has been noted [33].…”
Section: Discussionmentioning
confidence: 87%
See 1 more Smart Citation
“…Our previous study [2] has also indicated that at a concentration of 10 nM, dofetilide has no rate-dependent effect (reverse use-dependence), which is further confirmed by the present study. This concentration of dofetilide is within peak plasma concentrations, which are in the range of 1.74-5.11 ng/ml (i.e., 3.9-11.6 nM) following a loading infusion [14]. At high doses of dofetilide, a slight decrease or reversal of its class III effects has been noted [33].…”
Section: Discussionmentioning
confidence: 87%
“…The present study was, therefore, designed to answer the question of whether dofetilide, at a clinically relevant concentration [14,15], lengthens the actionpotential duration in the hyperkalemic zone as it does in the normokalemic zone in myocardium at various pacing frequencies. The electrophysiological effects of dofetilide were examined when both [K ÷ ]o and pacing cycle length were altered in isolated guinea-pig ventricular papillary muscle.…”
mentioning
confidence: 99%
“…T o date, information on the pharmacokinetics of dofetilide is limited to that obtained in man after intravenous administration (Sedgewick et al 1991, Gemmill et al 1991. In these studies the compound exhibited linear kinetics with mean plasma clearances of 4.7 and 5.2 ml/min per kg and mean terminal half-lives of 9.7 and 8.1 h. This paper reports the pharmacokinetics and metabolism in animals and man.…”
Section: Introductionmentioning
confidence: 99%
“…An extremely low incidence of noncardiac eff e c t s was reported by Sedgwick et al 38 and Connelly et al, 57 which consisted of increased flatulence, loose stools, and mild headaches. Cardiac adverse events have been primarily limited to ventricular tachycardia, most notably torsade de pointes.…”
Section: Adverse Effectsmentioning
confidence: 85%
“…6 A linear relation-ship exists between intravenous doses of dofetilide and both plasma concentrations and AUC. 38 The volume of distribution of dofetilide is approximately 3 L/kg. 27,28,37 Plasma protein binding of dofetilide is 64%.…”
Section: P H a R M A C O K I N E T I C Smentioning
confidence: 99%