PT  - JOURNAL ARTICLE
AU  - A Küpfer
AU  - G M Brilis
AU  - J T Watson
AU  - T M Harris
TI  - A major pathway of mephenytoin metabolism in man. Aromatic hydroxylation to p-hydroxymephenytoin.
DP  - 1980 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 1--4
VI  - 8
IP  - 1
4099  - http://dmd.aspetjournals.org/content/8/1/1.short
4100  - http://dmd.aspetjournals.org/content/8/1/1.full
SO  - Drug Metab Dispos1980 Jan 01; 8
AB  - A major metabolite of the antiepileptic drug mephenytoin (3-methyl-5-ethyl-5-phenylhydantoin) has been identified in urine after a single oral dose of 100 mg of mephenytoin in man. Using chemical synthesis, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy, we established its chemical structure as 3-methyl-5-ethyl-5-(4-hydroxyphenyl)hydantoin (4-OH-M) which is a product of aromatic hydroxylation of mephenytoin in man. Quantitative determinations of 4-OH-M in urine of 10 volunteers showed that 43 +/- 7% (SD) of a single oral dose of 100 mg of mephenytoin were eliminated as the glucuronide of this metabolite. Urinary elimination of the demethylated metabolite, 5-ethyl-5-phenylhydantoin (Nirvanol), was low (1% of the dose per 24 hr) emphasizing the importance of 4-OH-M as the major metabolite after a single oral dose of mephenytoin. Other products of mephenytoin hydroxylation (2-OH-M, E-OH-M, or aliphatically hydroxylated 2-OH-ethyl-M) were not detectable under the conditions selected (less than 1 mumol/24 hr).