DEBRISOQUINE AND METOPROLOL OXIDATION IN ZAMBIANS - A POPULATION STUDY

The 0-8 h urinary distributions of the metabolic ratios of debrisoquin e (10 mg) and metoprolol (100 mg) were measured in 102 healthy, unrela ted, black Zambian medical students. There was a statistically signifi cant correlation (r(s) = 0.60, p < 0.001; n = 88) between the debrisoq uine/4-hydroxydebrisoquine (D/HD) and metoprolol/alpha-hydroxymetoprol ol (M/HM) ratios. Bimodality in the distribution of the log10D/HD rati o was not evident from visual inspection and following kernel density analysis of the data, although two subjects (ratios 20, 22) would be c lassified as phenotypic poor metabolizers (PMs) based on the antimode used for Caucasian populations. The distribution of the log10M/HM rati o 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 v alue (greater-than-or-equal-to 302) of one individual had a profound i nfluence 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 deb risoquine (D/HD ratio 1.54). H117/04, the major metabolite of metoprol ol was also not detected in this sample. Since H117/04 was shown to be present in all samples from previous population studies, the possibil ity that this subject did not comply with the protocol could not be ex cluded. All other subjects had M/HM ratios less-than-or-equal-to 12.5. These findings suggest that there is a dissociation in the control of debrisoquine and metoprolol oxidation in Zambians as has been observe d previously in Nigerians. Furthermore, clear evidence that the metabo lism of these drugs exhibits genetic polymorphism in Zambians was not obtained.