(S)-Mephenytoin (Synonyms: (S)-5-Ethyl-3-methyl-5-phenylhydantoin)

S-Mephenytoin (5-phenyl-5-ethyl-N-methylhydantoin) is an anticonvulsive drug which is metabolized by N-demethylation and 4-hydroxylation (of the aromatic ring). CYP2C19 genotype is a major determined factor for metabolisms of S-Mephenytoin. The formations of 4X-hydroxymephenytoin, S-Mephenytoin’s metabolite is CYP2C19 genotype dependent.^[1][2]

The genetic polymorphism of CYP2C19 was revealed by the discovery of deficient 4’-hydroxylation of mephenytoin (3-methyl-5-phenyl-5 ethylhydantoin; Mesantoin). Human can be characterized as poor (PM) or extensive metabolizers (EM) with use of racemic mephenytoin as a phenotyping drug, and CYP2C19 has been identified as the major S-Mephenytoin (S-MP) hydroxylase in human. This polymorphism affects the metabolism of many other clinically important drugs such as diazepam, omeprazole (OP), imipramine, propranolol, and chloroguanide.^[1]

Rabbit anti-human cytochrome b5 inhibited NADH-cytochrome-c reductase and S-Mephenytoin 4-hydroxylase activities in human liver microsomes. In the presence of cytochrome b5, the Km value for S-Mephenytoin was 1.25 mM with all five purified cytochrome P-450s preparations, and Vmax values were 0.8-1.25 nmol of 4-hydroxy product formed per min/nmol of P-450. P-45OMP is a relatively selective P-450 form that metabolizes substituted hydantoins well.^[2]

References:
[1]. Zhou HH. CYP2C19 genotype determines enzyme activity and inducibility of S-Mephenytoin hydroxylase. Clin Chim Acta. 2001 Nov;313(1-2):203-8.
[2]. Shimada T, et al. Human liver microsomal cytochrome P-450 mephenytoin 4-hydroxylase, a prototype of genetic polymorphism in oxidative drug metabolism. Purification and characterization of two similar forms involved in the reaction. J Biol Chem. 1986 Jan 15;261(2):909-21.