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- ethyl-4-(2-nitrophenyl)-3,5-pyridined icarboxylate, Bay k 5552), a calcium antagonist, were investigated aft er administration of a single oral 10 mg dose and after 7 same doses o n consecutive days to hypertensive patients with normal renal function (NRF) and those with mild to moderate renal dysfunction (impair-ed re nal function, IRF). A significant decrease in blood pressure was obser ved after consecutive dosing of nisoldipine compared to baseline value s over 24 h in both groups. There were no significant differences in p lasma profiles of nisoldipine in both groups after either single oi co nsecutive 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 ifs active m etabolite in the NRF and IRF groups did not differ after the single an d the consecutive dosing. lit addition, there were neither prolongatio n of apparent elimination half-life (t(1/2)) nor increases in peak pla sma levels (C-max), ar the area under the plasma concentration-time cu rve (AUC(0-infinity)) after consecutive closing in both groups Cumulat ive urinary excretion rates of the major metabolites Bay s 4755 and Ba y s 1869, did not differ significantly between the NRF and IRF groups in both single and consecutive studies. In the present study, mild flu shing was observed in one patient with IRF. There was no deterioration in renal function during the study. These results suggest that nisold ipine may have a long-lasting antihypertensive effect during consecuti ve dosing and that it can be used in hypertensive patients regardless of presence of renal dysfunction.