Evidence for interethnic variations in the activity of CYP3A4

The CYP3A4 subfamily is involved in the metabolism of numerous drugs, including nifedipine, midazolam and cyclosporin. Oral nifedipine bioavailability has been reported to be higher in Mexican, South Asian and Nigerian healthy subjects compared to Caucasians. Oral cyclosporin and midazolam bioavailabilities are also higher in Mexicans than in Caucasians. Nifedipine bioavailability was similar in subjects maintained under typical Western, Indian or Mexican diets. Therefore, nutritional habits do not appear to be involved in the observed interethnic variations. Studies performed after iv administration of nifedipine have shown that South Asian and Mexican individuals show a decreased drug clearance compared to Caucasians, while volume of distribution does not vary among ethnic groups. There is also evidence that midazolam clearance in Mexicans is lower than in Caucasians. The data available at present suggest that CYP3A4 activity vary among ethnic groups, but that differences are not due to nutrition. Thus, it is likely that interethnic variations in drug clearance are due to genetically determined differences.