Debrisoquine and metoprolol oxidation in Zambians: a population study

The 0-8 h urinary distributions of the metabolic ratios of debrisoquine (10 mg) and metoprolol (100 mg) were measured in 102 healthy, unrelated, black Zambian medical students. There was a statistically significant correlation (rs = 0.60, p < 0.001; n = 88) between the debrisoquine/4-hydroxydebrisoquine (D/HD) and metoprolol/alpha-hydroxymetoprolol (M/HM) ratios. Bimodality in the distribution of the log10D/HD ratio was not evident from visual inspection and following kernel density analysis of the data, although two subjects (ratios 20, 22) would be classified as phenotypic poor metabolizers (PMs) based on the antimode used for Caucasian populations. The distribution of the log10M/HM ratio was skewed and on the basis of kernel density analysis, bimodal. It was clear from visual inspection of the data that the very high M/HM value (> or = 302) of one individual had a profound influence on the population M/HM ratio distribution. No HM was detected in the urine of this subject but he was not one of the two PMs of debrisoquine (D/HD ratio 1.54). H117/04, the major metabolite of metoprolol was also not detected in this sample. Since H117/04 was shown to be present in all samples from previous population studies, the possibility that this subject did not comply with the protocol could not be excluded. All other subjects had M/HM ratios < or = 12.5. These findings suggest that there is a dissociation in the control of debrisoquine and metoprolol oxidation in Zambians as has been observed previously in Nigerians. Furthermore, clear evidence that the metabolism of these drugs exhibits genetic polymorphism in Zambians was not obtained.