Mephenytoin hydroxylation deficiency in Caucasians: frequency of a new oxidative drug metabolism polymorphism

Clin Pharmacol Ther. 1984 Dec;36(6):773-80. doi: 10.1038/clpt.1984.256.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Chromatography, High Pressure Liquid
  • Debrisoquin / analogs & derivatives
  • Debrisoquin / metabolism
  • Debrisoquin / urine
  • Female
  • Humans
  • Hydantoins / metabolism*
  • Hydroxylation
  • Male
  • Mephenytoin / analogs & derivatives
  • Mephenytoin / metabolism*
  • Mephenytoin / urine
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic
  • Tennessee
  • White People*


  • Hydantoins
  • 4-hydroxydebrisoquin
  • 4-hydroxymephenytoin
  • Mephenytoin
  • Debrisoquin