Phenotyping polymorphic drug metabolism in the French Caucasian population

Eur J Clin Pharmacol. 1988;35(2):167-71. doi: 10.1007/BF00609247.

Abstract

Because of the large interethnic differences in the incidence of poor metabolizer phenotypes, French Caucasians have been studied for two independent polymorphisms, debrisoquine/dextromethorphan and mephenytoin metabolism. One hundred and thirty-two unrelated French Caucasians were phenotyped using oral doses of dextromethorphan 20 mg and mephenytoin 100 mg. Individual dextrorphan excretion over 8 h and the dextromethorphan/dextrorphan metabolic ratio were calculated. Extensive metabolizers were taken as subjects with a high dextrorphan output (15.56 mumol/8 h) and a low metabolic ratio (0.0023), and poor metabolizers were those with a low dextrorphan output (0.39 mumol/8 h) and a high metabolic ratio (7.00). Individual 4-hydroxymephenytoin excretion and mephenytoin hydroxylation indices were also determined. Extensive metabolizers eliminated large amounts of 4 hydroxymephenytoin (133.2 mumol/8 h) and had a hydroxylation index of 1.99, and poor metabolizers, because of impaired mephenytoin metabolism, had a high hydroxylation index (277). The incidence of the poor metabolizer phenotype was 3% for dextromethorphan (95% confidence limits 0.5%-8.5%) and 6% for mephenytoin (95% confidence limits 2%-12.5%).

MeSH terms

  • Adult
  • Dextromethorphan / metabolism*
  • Female
  • France
  • Humans
  • Hydantoins / metabolism*
  • Levorphanol / analogs & derivatives*
  • Male
  • Mephenytoin / analogs & derivatives
  • Mephenytoin / metabolism*
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*
  • Whites*

Substances

  • Hydantoins
  • Levorphanol
  • 4-hydroxymephenytoin
  • Dextromethorphan
  • Mephenytoin