title: Mephenytoin hydroxylation deficiency in Caucasians: frequency of a new oxidative drug metabolism polymorphism.
abstract: The ability of normal subjects to hydroxylate mephenytoin (100 mg) or debrisoquine (10 mg) after oral dosing was investigated in 156 unrelated Caucasians living in middle Tennessee. Urinary recovery of 4-hydroxymephenytoin (4-OH-M) and the urinary S:R enantiomeric ratio of mephenytoin measured in an 8-hr urine sample were investigated as phenotypic traits for mephenytoin, and the urinary metabolic ratio of debrisoquine was used to determine the debrisoquine hydroxylase phenotype. Both urinary 4-OH-M and the S:R ratio of mephenytoin discriminated between extensive (EM) and poor (PM) metabolizers of mephenytoin. The frequencies of PMs for mephenytoin and debrisoquine hydroxylation activity were 2.6% and 7.0%. These two defects in oxidative metabolism were not observed in the same subjects, which suggests that 4-hydroxylation of mephenytoin is a new polymorphism independent of that for debrisoquine.
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003647:Debrisoquin / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D005260:Female; D006801:Humans; D006827:Hydantoins / Q000378:metabolism*; D006900:Hydroxylation; D008297:Male; D008617:Mephenytoin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D013714:Tennessee; D044465:White People
chemical_list: D006827:Hydantoins; C012359:4-hydroxydebrisoquin; C025687:4-hydroxymephenytoin; D008617:Mephenytoin; D003647:Debrisoquin