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.

Metoprolol oxidation polymorphism in a Korean population: comparison with native Japanese and Chinese populations.

“…The results indicate that Koreans, like Japanese and Chinese, have a very low frequency of the PM phenotype of metoprolol oxidation compared with white British subjects (Iyun et al, 1986;McGourty et al, 1985).…”

“…We have recently reported that Japanese and mainland Chinese have a relatively low frequency of the PM phenotype for metoprolol oxidation (Horai et al, 1989) compared with a white British population (Iyun et al, 1986;McGourty et al, 1985), and that the metabolic capacity differs between the extensive metabolisers (EMs) of the two Oriental populations (Horai et al, 1989 . Statistical significance was defined as P < 0.05.…”

N‐acetylation phenotyping with dapsone in a mainland Chinese population.

“…Similarly, Carr et al (1978) phenotype three out of their 50 subjects and Clark (1985) found two subjects in over 100 individuals whose metabolic ratio would not allow accurate phenotyping. Clark (1985) (Ishizaki et al, 1987) and others (Iyun et al, 1986). Mass screening tests to define acetylator status in a selected population become more feasible and convenient if an adequate noninvasive procedure can be developed.…”

Interethnic Differences in Genetic Polymorphisms of CYP2D6 in the U.S. Population: Clinical Implications

“…Reports on the prevalence of PMs in African populations differ widely, with estimates varying in the range of 0%-19% [21,[35][36][37][38]. There is also a wide range in the incidence of PMs reported in African-Americans, 1.9%-7.3% [39][40][41][42].…”