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Mephenytoin hydroxylation deficiency in Caucasians: Frequency of a new oxidative drug metabolism polymorphism
Author(s) -
Wedlund P J,
Aslanian W S,
McAllister C B,
Wilkinson G R,
Branch R A
Publication year - 1984
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1984.256
Subject(s) - mephenytoin , debrisoquine , hydroxylation , urine , urinary system , pharmacogenetics , chemistry , pharmacology , medicine , endocrinology , biochemistry , biology , genotype , enzyme , gene
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. Clinical Pharmacology and Therapeutics (1984) 36 , 773–780; doi: 10.1038/clpt.1984.256