Phenylbutazone-warfarin interaction in the dog

The administration of phenylbutazone together with warfarin to dogs resulted in an elevation of the free fraction of warfarin in the plasma from 2-6 to 8-0% thus providing direct support for the notion that phenylbutazone induced inhibition of warfarin binding to plasma proteins. This inhibition as evaluated by a kinetic method was accompanied by a two-fold decrease in the plasma half-life of warfarin from 18-4 h in control animals to 9-6 h in phenylbutazone-treated animals. Marked increases in warfarin-induced hypoprothrombinaemia were observed when at doses up to 8 mg kg-1 (orally) it was given with phenylbutazone (50 mg kg-1, orally). The unbound fraction of warfarin in canine plasma ranged from 1-7 to 4-3% indicating individual differences in the extent of the plasma binding of warfarin in the dog.