Total and free steady-state plasma levels and pharmacokinetics of nifedipine in patients with terminal renal failure

Summary

The total and free steady-state plasma levels of nifedipine in patients with renal failure have been compared with those in subjects with normal renal function. Studies were done after administration of nifedipine 10 mg t.d.s. p.o. for 5 days, after i.v. infusion of 4·4 mg, and after a single 10 mg oral dose.

The systemic clearance of nifedipine after a single i.v.-dose was higher in subjects with renal insufficiency (854 ml/min) than in those with normal renal function (468 ml/min). After the single oral dose the AUC (6100 ng·min·ml⁻¹) and maximum plasma concentration (75.0 ng·ml⁻¹) were lower than in subjects with normal renal function (19300 ng·ml⁻¹; 122 ng·ml⁻¹). The plasma protein binding of nifedipine averaged 95.5% in normal subjects and 94.8% in patients with renal failure.

Although free and total steady-state plasma levels of nifedipine tended to be somewhat lower than normal in renal failure, the changes in pharmacokinetics and decreased protein binding of nifedipine did not result in a significantly different steady-state plasma level of the drug. The blood pressure response to a given plasma nifedipine level appeared to be enhanced in renal failure.