SCREENING FOR CYTOCHROME-P450 3A IN MAN - STUDIES WITH MIDAZOLAM AND NIFEDIPINE

This report describes work directed towards the development of a scree ning technique for cytochrome P450 3A activity which should be valid f or a variety of drugs metabolized by this enzyme. A significant correl ation (P < 0.01) was found between the ratio of the plasma concentrati on of nifedipine to that of its oxidized metabolite and the area under the time curve for the plasma concentration of midazolam. It is sugge sted that the nifedipine:metabolite ratio might have general predictiv e value for the metabolism of orally administered cytochrome P450 3A s ubstrates.