Metoprolol α-Hydroxylation Polymorphism in the San Bushmen of Southern Africa

1. The metabolic oxidation of metoprolol has been studied in a group of 98 San Bushmen. 2. The amounts of metoprolol and alpha-hydroxy metoprolol excreted in 0-8 h urine collection, after dosing with 100 mg metoprolol, were measured and the metabolic ratio (% dose excreted as metoprolol/% dose excreted as alpha-hydroxy metoprolol) calculated. 3. Frequency distribution and probit plots of the metabolic rate data showed a bimodal distribution with 4.1% of the population exhibiting slow metabolism with an MR greater than 10. 4. These results are much less than found in Caucasians (8.4%) but very different from the unimodal distribution found for Nigerians. 5. A previous study in the same group of Bushmen had revealed that 18 of 96 subjects were poor or non-metabolizers of debrisoquine to 4-hydroxy debrisoquine, but only one of the poor metoprolol metabolizers was a poor metabolizer of debrisoquine. 6. On the basis of these results, the claim of debrisoquine type of polymorphism for beta-adrenoceptor antagonists found in Caucasians cannot be extrapolated to the San Bushmen, and one must query the use of debrisoquine as measure of oxidative status in any group other than Caucasians.