[Individual difference in drug metabolism--pharmacogenetical approach]

Differences in individual susceptibility to some kind of drug are mainly attributable to genetically determined differences in metabolic capability, although other factors, such as pathways of absorption, distribution and excretion, are important. A man, who has an impaired ability of the metabolism of a drug, responds sensitively to adverse effects of the drug. Recently, a development on assays of drug oxidation reactions shows that a frequency of occurrence in poor metabolizers in the population is observed differently in various ethnic groups. For example, in the metabolism of debrisoquine, an antihypertensive drug, the frequency in the British and the Nigerian is around 8-9%, while that in the Saudi Arabian and the Egyptian is 1%. To measure the oxidation status for debrisoquine is found to be useful tool for determining individual capability to oxidize various kinds of drugs. The cancer group contains a disproportionately large number of individuals who are extensive oxidizers compared to the control. Since most carcinogens require metabolic oxidation to generate reactive intemediates, which interact with nucleophiles in the cell, an assumption arises that there may be an association between genetically determined oxidation status and propensity to develop tumors in response to carcinogens in the environment.