Warfarin-phenylbutazone interaction in man: a long term multiple dose study

Abstract

The effect of phenylbutazone on the disposition of warfarin was studied in a subject given warfarin daily for one month. During concomitant phenylbutazone administration, the total plasma warfarin concentration declined from 4.2 to 2.0 mg/L. In contrast, the unbound warfarin plasma concentration rose from 0.020 to 0.033 mg/L. The plasma concentration and daily urinary excretion of 7-hydroxywarfarin fell during phenylbutazone administration. Warfarin is administered as a racemate. Exclusive to and the major metabolic route of the more potent S-isomer is 7-hydroxylation. It is concluded that inhibition of S-warfarin metabolism can help explain the increased anticoagulation seen when phenylbutazone is added to the dosage regimen of a patient stabilized on warfarin.