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

Clinical Pharmacology and Therapeutics
A O IyunH F Woods

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 ...Continue Reading

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