(R)-Mephenytoin is the (R) enantiomer of the anticonvulsant mephenytoin.[1] (R)-Mephenytoin can be demethylated by the cytochrome P450 (CYP) isoform CYP2C9 to form the active metabolite 5-ethyl-5-phenylhydantoin (nirvanol). [2][3]The ratio of (S)-mephenytoin to (R)-mephenytoin in urine following administration of the racemic mixture has been used to detect polymorphisms in drug metabolism by CYP2C19, as only (S)-mephenytoin is a substrate of CYP2C19.[4][5][2]
Reference:
[1]. Meier, U.T., Kronbach, T., and Meyer, U.A. Assay of mephenytoin metabolism in human liver microsomes by high-performance liquid chromatography. Anal. Biochem. 151(2), 286-291 (1985).
[2]. Lewis, D.F., Dickins, M., Weaver, R.J., et al. Molecular modelling of human CYP2C subfamily enzymes CYP2C9 and CYP2C19: Rationalization of substrate specificity and site-directed mutagenesis experiments in the CYP2C subfamily. Xenobiotica. 28(3), 235-268 (1998).
[3]. Wong, P.T.H., Tan, S.F., and Lee, H.S. N-demethylation of methyl and dimethyl derivatives of phenytoin and their anticonvulsant activities in mice. Japanese Journal of Pharmacology 48(4), 473-478 (1988).
[4]. Ferguson, R.J., de Morais, S.M., Benhamou, S., et al. A new genetic defect in human CYP2C19: Mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin. Journal of Pharmacology and Experimental Therapeutics 284(1), 356-361 (1998).
[5]. Guttendorf, R.J., Britto, M., Blouin, R.A., et al. Rapid screening for polymorphisms in dextromethorphan and mephenytoin metabolism. British Journal of Clinical Pharmacology 29(4), 373-380 (1990).