Shionoiri H, Minamisawa K, Masumori S, Satta H, Minamisawa M, Takizawa T, Jinno Y, Takeda K, Nagasawa T, Takasaki I
Second Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Arzneimittelforschung. 1995 Jul;45(7):785-9.
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.
对肾功能正常（NRF）和轻度至中度肾功能不全（肾功能受损，IRF）的高血压患者，单次口服10mg剂量以及连续7天服用相同剂量后，研究了钙拮抗剂尼索地平（CAS 63675 - 72 - 9，1,4 - 二氢 - 2,6 - 二甲基 - 4 -（2 - 硝基苯基）- 3,5 - 吡啶二甲酸异丁酯甲酯，Bay k 5552）的药代动力学和药效学。与基线值相比，两组连续服用尼索地平24小时后血压均显著下降。单次或连续给药后，两组尼索地平的血浆曲线无显著差异。活性代谢产物Bay r 9425的血浆浓度 - 时间曲线在两组中与尼索地平相似。单次和连续给药后，NRF组和IRF组中尼索地平及其活性代谢产物的药代动力学参数无差异。此外，两组连续给药后，表观消除半衰期（t1/2）均未延长，血浆峰值水平（Cmax）或血浆浓度 - 时间曲线下面积（AUC0 - ∞）均未增加。单次和连续研究中，NRF组和IRF组主要代谢产物Bay s 4755和Bay s 1869的累积尿排泄率无显著差异。在本研究中，一名IRF患者出现轻度潮红。研究期间肾功能无恶化。这些结果表明，连续给药期间尼索地平可能具有持久的降压作用，且无论是否存在肾功能不全，均可用于高血压患者。
