Stereoselective metabolism and disposition of the enantiomers of mephenytoin during chronic oral administration of the racemic drug in man.

Abstract

The stereospecific disposition of the enantiomers of mephenytoin has been investigated during chronic oral administration of racemic mephenytoin (23 μmol/kg/day) for 14 days in four normal subjects. On days 1 and 11, 5 μCi of [14C]-S-mephenytoin and 45 μCi of [3H]-R-mephenytoin were administered concomitantly with unlabeled racemic mephenytoin. Plasma mephenytoin concentrations reached a peak on the 2nd day of administration, then declined to a plateau between the 7th and 14th day. Mephenytoin was metabolized to two major metabolites. Firstly, 4-hydroxylation of the phenyl ring [3-methyl-5-(4-hydroxy phenyl)-5-ethylhydantoin; 4-OH-M) yielded a metabolite which was rapidly eliminated in urine..