The polymorphic 4-hydroxylation of debrisoquine in a Saudi arab population.

1. Debrisoquine 4-hydroxylation was polymorphic in 102 Saudi arab volunteers, the population comprising one phenotypically poor metabolizer and 101 phenotypically extensive metabolizers of debrisoquine. 2. Mean urinary recoveries of drug and metabolite were low in Saudis (15 +/- 10% dose, mean +/- S.D.), which compared well with previously studied populations of Egyptians (16%) and Ghanaians (18%), but which were lower than those seen in a UK white population (41%). 3. Saudis, like Egyptians, were more extensive metabolizers of debrisoquine than UK whites, as judged by the metabolic ratio (% dose as debrisoquine/% dose as 4-hydroxy-debrisoquine eliminated in the urine). 4. Neither sex, urine collection period nor urinary recovery of drug and metabolite had any statistically significant effect upon the distribution of metabolic ratios in Saudis. 5. The frequency of the DL allele controlling the recessive poor metabolizer trait was 0.099 +/- 0.049 (+/- S.E.M.) in Saudis, which compared well to Egyptians (0.118 +/- 0.059) but was significantly lower than that for UK whites (0.298 +/- 0.030). 6. These findings raise questions regarding the efficacy and safety in Saudis of drugs undergoing oxidative metabolism which have been evaluated for usage in European white subjects.