EFFECTS OF AGING AND GENDER ON CYTOCHROME P450 ACTIVITY--SUSTAINED RELEASE DOSE

$0M01FY2000RRNIH

Northwestern University, Evanston IL

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Abstract

This study is a continuation of the investigations of the P.I. to evaluate in vivo probes of human drug metabolism by the major isoform of the cytochrome P450 (CYP3A) system in order to determine the effects of aging, gender, and disease states on hepatic drug metabolism with the ultimate goal of developing better guidelines for drug dosing in the elderly. In this study we well determine the effects of known cytochrome P450 inhibitors and inducers on the clearance of verapamil (an antihypertensive drug of the calcium antagonist group which undergoes metabolism by CYP3A in approximately 70 healthy young (20-40 yr.) and elderly (>60 yr.) men and women. As sub-analyses, we will also determine the effects of aging on hepatic CYP induction, the correlation between verapamil clearance and the 14C-erythromycin breath test (as another CYP450 probe), and differentiate between the effects on verapamil clearance of CYP3A inhibition at the gut (grapefruit juice) and in the liver and gut (itraconazole).

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