Effect of digoxin on plasma clearance and anticoagulant effect of warfarin in rats

The possible effects of digoxin on the elimination and anticoagulant action of warfarin were examined in rats. The pharmacokinetic parameters of warfarin after a single i.v. (1.2 mg/kg) or repeated oral coadministration with anticoagulant (0.6 mg/kg on day 1, thereafter 0.3 mg/kg) and digoxin (50 micrograms/kg) were not significantly different as compared with those in the group treated with warfarin alone. However, prothrombin complex activity (PCA) following coadministration with the diuretic was significantly and relatively rapidly recovered as compared with that in the warfarin group. The amounts of warfarin extracted by liver 2 and 6 h after a single i.v. dosing or 3 and 8 h after repeated oral dosing in the coadministered group were significantly decreased as compared with those in the group received warfarin alone. The renal function (renal plasma flow rate (RPF) and glomerular filtration rate) in the group coadministered with digoxin was significantly higher than that in the group receiving warfarin alone. On the other hand, the fraction of warfarin bound to BSA or rat plasma and the plasma water were little changed in the presence of digoxin. These results suggest that a pharmacological interaction, the decrease in the anticoagulant action, is induced between warfarin and digoxin coadministered.