digoxin and azimilide

Antiarrhythmic drug therapy, broadly defined, is the mainstay of treatment and prevention of ventricular tachycardia (VT)/ventricular fibrillation (VF), which can lead to sudden death. This article evaluates the evidence for and appropriate use of class I antiarrhythmic drugs, class III antiarrhythmic drugs, beta-blockers, nondihydropyridine calcium-channel blockers, statins, angiotensin enzyme inhibitors, angiotensin receptor blockers, aldosterone blockers, and digoxin for antiarrhythmic benefits in patients who have a propensity for VT/VF and therefore are at risk of sudden death.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Carbazoles; Carvedilol; Digoxin; Heart Conduction System; Humans; Hydantoins; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Imidazolidines; Piperazines; Propanolamines; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Sotalol; Tachycardia, Ventricular

The influence of coadministration on digoxin and azimilide pharmacokinetics/pharmacodynamics was assessed in a randomized, 3-way crossover study in 18 healthy men. Serial blood and urine samples were obtained for azimilide and digoxin quantitation. Treatment effects on pharmacokinetics were assessed using analysis of variance. The relationship between azimilide blood concentrations and QT(c) prolongation was characterized by an E(max) model. Effects of coadministration on pharmacodynamics were assessed using a mechanistic-based inhibition model. Azimilide pharmacokinetics was unaffected by digoxin, except for a 36% increase in CL(r) (P = .0325), with no change in CL(o). Digoxin pharmacokinetics was unaffected by azimilide, except for a 21% increase in C(max) (P = .0176) and a 10% increase in AUC(tau) (P = .0121). Digoxin coadministration increased the apparent EC(50) with no effect on E(max), consistent with competitive inhibition (K(i) = 0.899 ng/mL). The pharmacokinetic and pharmacodynamic changes observed upon coadministration were small and are not expected to be clinically important.

Topics: Adolescent; Adult; Anti-Arrhythmia Agents; Cardiotonic Agents; Cross-Over Studies; Digoxin; Drug Combinations; Drug Interactions; Electrocardiography; Humans; Hydantoins; Imidazolidines; Male; Piperazines