Stereoselective metabolism and disposition of the enantiomers of mephenytoin during chronic oral administration of the racemic drug in man.
A Küpfer, PV Desmond, S Schenker, RA Branch
J Pharmacol Exp Ther | Published : 1982
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..View full abstract