Warfarin-phenylbutazone interaction in man: a long term multiple dose study.
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.
D000328:Adult; D004347:Drug Interactions; D006801:Humans; D006900:Hydroxylation; D008297:Male; D010653:Phenylbutazone / Q000494:pharmacology*; D013997:Time Factors; D014859:Warfarin / Q000378:metabolism / Q000494:pharmacology*
D014859:Warfarin; D010653:Phenylbutazone