Phenylbutazone-warfarin interaction in the dog

Abstract

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.