INFLUENCE OF RENAL-FAILURE ON CYTOCHROME-P-450 ACTIVITY IN HYPERTENSIVE PATIENTS USING A COCKTAIL OF ANTIPYRINE AND NIFEDIPINE

Objective. Two substrates were coadministered in a ''cocktail'' approa ch to evaluate the contribution of renal failure to drug oxidation. Pa tients. Nineteen hypertensive patients, nine of them with chronic rena l failure (CL(CR) 38.9 vs 102.3 ml . min(-1). 1.73 m(-2)), were invest igated after peroral administration of a combination of antipyrine (50 0 mg, in capsules) and nifedipine (10 mg, in Oxcord capsules) in the m orning after an overnight fast. Results. This ''cocktail'' approach ma de it possible to characterize in vivo the activities of different for ms of cytochrome P-450 in a single-study protocol using the total clea rance of nifedipine and clearance for production of 3-hydroxymethylant ipyrine (HMA), 4-hydroxyantipyrine (OHA) and norantipyrine (NORA). Wit h this ''cocktail'' approach (antipyrine plus nifedipine), we can sugg est a selective effect on the activities of cytochrome P-450 forms ass ociated with the formation of dehydronifedipine (P-450 III A(4)) and o f NORA in patients with mild renal failure under long-term antihyperte nsive therapy.