Dapsone N-acetylation, metoprolol alpha-hydroxylation, and S-mephenytoin 4-hydroxylation polymorphisms in an Indonesian population: a cocktail and extended phenotyping assessment trial

Clin Pharmacol Ther. 1994 Aug;56(2):142-53. doi: 10.1038/clpt.1994.117.

Abstract

We examined dapsone N-acetylation and metoprolol alpha-hydroxylation and S-mephenytoin 4-hydroxylation phenotypings using the respective test probes (dapsone and racemic metoprolol and mephenytoin) administered separately and in a cocktail manner to an Indonesian subject group (n = 30). After ascertaining that the separate and cocktail phenotyping tests of the probe drugs correlated with each other (all rs values > 0.84; p < 0.001), the cocktail phenotyping assessment was extended to the other 74 Indonesians. In a total of 104 Indonesians phenotyped with the cocktail test, a visual antimode was apparent only in the dapsone N-acetylation and S-mephenytoin 4-hydroxylation polymorphisms: the frequencies of slow acetylators and poor hydroxylators were 43.3% (95% confidence interval, 33.7% to 52.8%) and 15.4% (95% confidence interval, 8.5% to 22.3%), respectively. The distribution histogram and probit plots of the metabolic ratio of metoprolol gave no clear evidence for bimodality, and therefore no poor alpha-hydroxylator of metoprolol was considered to exist in the present sample size. The findings indicate that the Indonesian subjects have a greater incidence of slow acetylator phenotype compared with Japanese and Chinese, as well as a frequency of poor metabolizer phenotype of S-mephenytoin similar to that of Korean and Chinese subjects. They resemble an African population (Nigerians) in metoprolol alpha-hydroxylation polymorphism, with no apparent antimode derived from white populations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adolescent
  • Adult
  • Asian People / genetics*
  • China
  • Dapsone / administration & dosage
  • Dapsone / blood
  • Dapsone / metabolism*
  • Female
  • Humans
  • Hydroxylation
  • Indonesia
  • Japan
  • Male
  • Mephenytoin / administration & dosage
  • Mephenytoin / blood
  • Mephenytoin / metabolism*
  • Metoprolol / administration & dosage
  • Metoprolol / blood
  • Metoprolol / metabolism*
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic / genetics

Substances

  • Dapsone
  • Metoprolol
  • Mephenytoin