Probenecid Phenprocoumon

Mbnig H, Bbhm MI, Ohnhaus EE, Kirch W. The effects of frusemide and probenecid on the pharmacokinetics of phenprocoumon. EurJ Clin Pharmacol (1990) 39, 261-5. 

In healthy subjects, probenecid increased the clearance of singledose phenprocoumon without altering its anticoagulant effect. The anticoagulant effects of multiple-dose phenprocoumon might be expected to be decreased by probenecid, but this requires confirmation. 

In 9 healthy subjects probenecid 500 mg four times daily for 7 days reduced the AUC of a single 0.22-mg/kg dose of phenprocoumon given on day one by 47% and reduced the elimination half-life by about one-third. Nevertheless, the reduction in prothrombin time by phenprocoumon was not altered by probenecid. ... 

The reasons for this interaction are not understood, but one possibility is that, while probenecid inhibits the glucuronidation of phenprocoumon (its normal route of metabolism), it may also increase the formation of hy-droxylated metabolites so that its overall loss is increased. ... 

---