The effect of different oral anticoagulants on diphenylhydantoin (DPH) and tolbutamide metabolism.

The effect of bishydroxycoumarin, phenprocoumon, warfarin and phenindione on the metabolism of diphenylhydantoin (DPH) and tolbutamide has been studied in 54 patients. The half-lives of DPH and tolbutamide in blood following i.v. injections were studied in 33 patients before and after one week of anticoagulant treatment. Bishydroxycoumarin increased the mean half-life values of DPH from 8.8 to 37.4 hours and of tolbutamide from 4.9 to 17.5. Phenprocoumon prolonged DPH half-life from a mean value of 9.9 to 14.0 hours but did not change the tolbutamide half-life. Warfarin and phenindione did not affect DPH or tolbutamide half-lives. Steady state concentration studies in 21 patients showed a rise in serum DPH during bishydroxycoumarin and phenprocoumon treatment but not during treatment with warfarin and phenindione. A rise in serum tolbutamide was noted during treatment with bishydroxycoumarin. These findings suggest that bishydroxycoumarin inhibits the betabolism of DPH and tolbutamide and that phenprocoumon inhibits DPH metabolism. No effect on DPH and tolbutamide metabolism could be demonstrated following administration of warfarin and phenindione.