The effects of frusemide and probenecid on the pharmacokinetics of phenprocoumon

We have studied the pharmacokinetics of phenprocoumon with and without co-administration of frusemide and probenecid in two groups of 17 healthy volunteers. Frusemide 40 mg b.i.d. for 7 days did not interact with phenprocoumon to a significant extent. Probenecid 500 mg q.i.d. for 7 days significantly accelerated the overall elimination of phenprocoumon, as indicated by a decrease in AUC from 295 to 157 micrograms.h.ml-1, and a reduction in the fraction of the dose excreted by the kidneys. The data are consistent with inhibition of the glucuronidation of phenprocoumon by probenecid. Its accelerated elimination may be a consequence of the increased formation of hydroxylated metabolites.