Interaction of d-propoxyphene and diphenylhydantoin in rat liver microsomal preparation.

Inhibition of diphenylhydantoin biotransformation by d-propoxyphene and the ihibition of d-propoxyphene metabolism by diphenylhydantoin was studied in rat liver microsomal 9000 x g supernatant preparations. The parahydroxylation of diphenylhydantoin was inhibited 98% by 5 x 10(-4)M concentration of d-propoxyphene in a noncompetitive manner with a Kj of 3.2 +/- 1.6 x 10(-5)M. Only 18% inhibition of the N-demethylation of d-propoxyphene was observed at clinically unrealistic diphenylhydantoin concentrations of 10(-3)M. The in vitro studies suggest that the inhibition of diphenylhydantoin metabolism by d-propoxyphene may result in toxicity when the two drugs are chronically administered together.