Effect of propafenone on digoxin kinetics in dogs

ABSTRACT

The effect of short-term treatment with propafenone on IV bolus digoxin kinetics has been investigated in six normal dogs. A dose of 0.05 mg/kg IV digoxin was given to each dog and blood samples were collected for digoxin assay. The dogs were then given propafenone orally in a dose of 40 mg/kg daily for ten days followed by the same IV bolus dose of digoxin, and blood samples were recollected for digoxin assay. The results showed that the distribution pharmacokinetic parameters of digoxin; namely, the central [Vc] and apparent [Vd] volumes of distribution and the distribution half life [T1/2 alpha] did not significantly change by propafenone treatment. However, the elimination half life [T1/2 beta] was significantly increased by 36.7% [p <0.05] as a result of the significant reduction in digoxin total body clearance by 28.4% [p <0.01]. This led to 37.1% increase [p <0.05] in the area under digoxin concentration time curve [AUC]