Influence of renal failure on cytochrome P450 activity in hypertensive patients using a “cocktail” of antipyrine and nifedipine

Abstract.

Objective. Two substrates were coadministered in a “cocktail” approach to evaluate the contribution of renal failure to drug oxidation.

Patients.

Nineteen hypertensive patients, nine of them with chronic renal failure (CL_CR 38.9 vs 102.3 ml⋅min⁻¹⋅1.73 m⁻²), were investigated after peroral administration of a combination of antipyrine (500 mg, in capsules) and nifedipine (10 mg, in Oxcord capsules) in the morning after an overnight fast.

Results.

This “cocktail” approach made it possible to characterize in vivo the activities of different forms of cytochrome P₄₅₀ in a single-study protocol using the total clearance of nifedipine and clearance for production of 3-hydroxymethylantipyrine (HMA), 4-hydroxyantipyrine (OHA) and norantipyrine (NORA). With this “cocktail” approach (antipyrine plus nifedipine), we can suggest a selective effect on the activities of cytochrome P₄₅₀ forms associated with the formation of dehydronifedipine (P₄₅₀ III A₄) and of NORA in patients with mild renal failure under long-term antihypertensive therapy.