Pharmacokinetics and pharmacodynamics of nisoldipine in hypertensive patients with normal and mild to moderate impaired renal function.

The pharmacokinetics and pharmacodynamics of nisoldipine (CAS 63675-72-9, isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, Bay k 5552), a calcium antagonist, were investigated after administration of a single oral 10 mg dose and after 7 same doses on consecutive days to hypertensive patients with normal renal function (NRF) and those with mild to moderate renal dysfunction (impaired renal function, IRF). A significant decrease in blood pressure was observed after consecutive dosing of nisoldipine compared to baseline values over 24 h in both groups. There were no significant differences in plasma profiles of nisoldipine in both groups after either single or consecutive dosing. The plasma concentration-time profiles of the active metabolite, Bay r 9425, were similar to those of nisoldipine in both groups. The pharmacokinetic parameters of nisoldipine and its active metabolite in the NRF and IRF groups did not differ after the single and the consecutive dosing. In addition, there were neither prolongation of apparent elimination half-life (t1/2), nor increases in peak plasma levels (Cmax), or the area under the plasma concentration-time curve (AUC0-infinity) after consecutive dosing in both groups. Cumulative urinary excretion rates of the major metabolites, Bay s 4755 and Bay s 1869, did not differ significantly between the NRF and IRF groups in both single and consecutive studies. In the present study, mild flushing was observed in one patient with IRF. There was no deterioration in renal function during the study. These results suggest that nisoldipine may have a long-lasting antihypertensive effect during consecutive dosing and that it can be used in hypertensive patients regardless of presence of renal dysfunction.