Relationship between mephenytoin oxidation polymorphism and phenytoin, methylphenytoin and phenobarbitone hydroxylation assessed in a phenotyped panel of healthy subjects

Br J Clin Pharmacol. 1990 Jun;29(6):665-71. doi: 10.1111/j.1365-2125.1990.tb03687.x.


1. In a phenotyped panel of healthy subjects correlations were studied between the oxidation of mephenytoin, phenytoin, methylphenytoin and phenobarbitone, with respect to the formation of their 4-hydroxy metabolites (OH-). 2. On different occasions phenotyped extensive metabolizers (EM; n = 16) and poor metabolizers (PM; n = 4) of mephenytoin received phenytoin (100 mg), methylphenytoin (100 mg) and phenobarbitone (50 mg) and urine was collected up to 24 h. The excreted 4-hydroxy metabolites of all compounds were measured by h.p.l.c. 3. Urinary recovery of OH-phenytoin was 31.0 +/- 11.7%, of OH-methylphenytoin 3.4 +/- 2.7% and of OH-phenobarbitone 1.4 +/- 1.2%. No correlation was found between the recovery of OH-mephenytoin and OH-phenytoin. A subject who produced virtually no OH-phenytoin was an EM of mephenytoin, confirming a dissociation of mephenytoin polymorphism and phenytoin hydroxylation. 4. The correlation coefficient for OH-mephenytoin and OH-methylphenytoin recovery was 0.71 (Spearman rank, P = 0.002). The PMs of mephenytoin excreted the least amount of OH-methylphenytoin, suggesting a cosegregation of the 4-hydroxylation pathways. No correlation was found between the urinary recovery of OH-phenobarbitone and that of the other 4-hydroxy metabolites.

MeSH terms

  • Adult
  • Female
  • Humans
  • Hydantoins / metabolism*
  • Hydroxylation
  • Male
  • Mephenytoin / metabolism*
  • Oxidation-Reduction
  • Phenobarbital / metabolism*
  • Phenotype
  • Phenytoin / metabolism*


  • Hydantoins
  • Phenytoin
  • Mephenytoin
  • Phenobarbital