Pharmacoanthropology: drug metabolism

This is a report of similarities and differences among various ethnically defined populations with respect to their capacities to metabolize the prototype drugs antipyrine, caffeine, and debrisoquine. There were equal levels of the three main metabolites of antipyrine in the urine of Caucasians and Orientals; differences in antipyrine clearance between English and Indian subjects appeared to have environmental causes. Exploration of various metabolite ratios of caffeine in the urine of Caucasians and Orientals living in Canada showed three patterns: 1) no interethnic difference occurred in the ratio thought to indicate xanthine oxidase activity; 2) products of 7-demethylation and of hydroxylation of paraxanthine , both probably produced by cytochrome P-450, showed different averages in the populations; 3) the new secondary metabolite acetylformyl -methyluracil proved to be a useful indicator of the genetically controlled acetylator status, thereby confirming the well-known population difference for acetylator gene frequency. Analysis of data on debriosquine hydroxylation suggested that interpretation of the standardized metabolic ratio may be appropriate for Caucasian and Oriental groups but is misleading for published data from Saudi Arabia, Nigeria, and Ghana; even these two closely related West African populations seem to differ in debrisoquine metabolism.