Interaction between warfarin and propafenone in healthy volunteer subjects

The effect of propafenone on the pharmacokinetics and pharmacologic effects of warfarin was studied in healthy normal male volunteer subjects. Each drug was administered alone for 1 week followed by a combined administration for 1 additional week. Blood samples were analyzed for propafenone and warfarin concentrations and the effect of each treatment on the prothrombin time was assessed. The concurrent administration of warfarin did not produce any changes in the absorption or disposition kinetics of propafenone. Concurrent propafenone administration did lead to a reduction in the clearance of warfarin, resulting in an average increase of 38% in the mean steady-state plasma warfarin concentration. During the combined therapy phase, the prothrombin time increased significantly (P less than 0.01) from the "warfarin alone" phase. We conclude from this study that the concomitant administration of propafenone and warfarin may lead to an enhanced anticoagulant effect that may require a reduction in the warfarin dose.