INHIBITION OF PHENYTOIN METABOLISM BY SULTHIAME IN EPILEPTIC PATIENTS

Abstract

1 Measurements have been made of steady state serum phenytoin concentration, serum half-life of (14)C-labelled phenytoin, and the urinary ratio of the major metabolite of phenytoin to the unchanged drug (p-HPPH: DPH ratio) in epileptic patients on and off sulthiame therapy. 2 Starting sulthiame treatment produced an increase in serum phenytoin concentration, a prolongation of the half-life and an increase in the p-HPPH: DPH ratio. The total urinary output of phenytoin plus p-HPPH was unaltered by sulthiame. 3 The results indicate that sulthiame or one of its metabolites inhibits the parahydroxylation of phenytoin by hepatic enzymes.