Effect of phenylbutazone on the metabolic disposition of warfarin in the dog.

Phenylbutazone has been shown to modify the physiologic disposition of warfarin in the dog. Dogs pretreated with phenylbutazone for a week, and permitted to remain drug-free for an additional week, eliminated warfarin from plasma 2-3 times faster than non-pretreated controls with an average half-life of 7.8 hours. In-vitro hepatic microsomal metabolism of warfarin and cytochrome P-450 content were greater for hepatic microsomes derived from phenylbutazone pretreated animals.