Evidence for a dissociation in the control of sparteine, debrisoquine and metoprolol metabolism in Nigerians

Pharmacogenetics. 1992 Apr;2(2):89-92. doi: 10.1097/00008571-199204000-00006.

Abstract

The 0-8 hour urinary distributions of the metabolic ratios of sparteine (100 mg), debrisoquine (10 mg) and metoprolol (100 mg) were measured in 165 healthy, unrelated, black Nigerian medical students. There was a weak correlation (rs = 0.51, p < 0.001; n = 82) between the metoprolol/alpha-hydroxymetoprolol (M/HM) and the sparteine/total (2- + 5-) dehydrosparteine (S/DHS) ratios. No significant correlations were found between the debrisoquine/4-hydroxydebrisoquine (D/HD) and M/HM ratios (rs = 0.16, n = 33) and between the D/HD and S/DHS ratios (rs = 0.31, n = 38). Both visual inspection and kernel density analysis of the data suggested the presence of two phenotypic groups for sparteine oxidation, with 4% of the population studied being putative poor metabolizers. In contrast biomodality was not apparent in the distribution of the log10M/HM and log10D/HD ratios. These findings provide evidence for a dissociation in the control of metoprolol, sparteine and debrisoquine oxidation in Nigerians and highlight the difficulties in the interpretation of data from pharmacogenetic studies in different ethnic groups.

MeSH terms

  • Adult
  • Black People / genetics
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Debrisoquin / metabolism*
  • Female
  • Gene Frequency
  • Humans
  • Male
  • Metoprolol / metabolism*
  • Mixed Function Oxygenases / genetics
  • Mixed Function Oxygenases / metabolism
  • Nigeria
  • Phenotype
  • Polymorphism, Genetic
  • Sparteine / metabolism*

Substances

  • Sparteine
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Cytochrome P-450 CYP2D6
  • Metoprolol
  • Debrisoquin