Pharmacokinetic analysis of potentiating effect of phenylbutazone on anticoagulant action of warfarin in man.

Warfarin is eliminated more rapidly but its anticoagulant effect is increased by concomitant administration of phenylbutazone. Pharmacokinetic analysis by recently developed techniues shows that the prewarfarin synthesis rate and the normal degradation of prothrombin complex activity are not affected by phenylbutazone, but that this drug has a pronounced effect on the relationship between synthesis rate of prothrombin complex activity and plasma-warfarin concentration. These observations are consistent with the assumption that phenylbutazone competitively displaces warfarin from nonspecific binding sites in the plasma and tissues (particularly the liver) and thereby increases the interaction of the anticoagulant with its pharmacologic receptor and metabolizing enzyme system.