Metoprolol and debrisoquin metabolism in Nigerians: lack of evidence for polymorphic oxidation

Abstract

The role of genetic polymorphism in the oxidative metabolism of metoprolol and debrisoquin was investigated in a population of 138 unrelated Nigerians. The debrisoquin/4-hydroxydebrisoquin 0-8 hour urinary ratio (D/HD) correlated significantly with the metoprolol/alpha-hydroxymetoprolol 0-8 hour urinary ratio (M/HM) (rs = 0.54; P less than 0.001), the metoprolol/H117-04 [4-(2-hydroxy-3-isopropylaminopropoxy)-phenylacetic acid] 0-8 hour urinary ratio (M/H117-04) (rs = 0.42; P less than 0.001), and the plasma metoprolol concentration at 3 hours (rs = 0.48; P less than 0.01). Both the median D/HD and M/HM ratios were significantly higher in this population than in a previously studied population of white British subjects. According to criteria established in studies of white populations, only one subject, later identified as an Indian, would be classified unequivocally as a poor metabolizer of both metoprolol and debrisoquin. All the other subjects were black Africans. Bimodality in the frequency distribution of both the log10 M/HM and D/HD ratios was not apparent. The poor hydroxylation trait may, therefore, be present at a lower frequency than in whites, absent altogether, or obscured by other factors. In ethnic studies of drug metabolism each racial group should be examined separately for evidence of polymorphic metabolism and antimodes should not be extrapolated from one population to another.