Davidsson G K, Edwards J S, Davidson C
Birch Hill Hospital, Rochdale, England.
Curr Med Res Opin. 1995;13(5):285-97. doi: 10.1185/03007999509111554.
Two studies were performed-one in elderly, hypertensive patients and one in patients with chronic liver disease-to investigate the effect of age and liver disease upon the pharmacokinetics of nisoldipine, a dihydropyridine-type calcium antagonist. The effect of acute and chronic administration of nisoldipine (once and twice daily) was investigated in 17 elderly hypertensive patients. Compared with previously published data from young healthy volunteers, the values for Cmax and AUC appear to be higher in elderly hypertensive patients while Tmax and half-life were unchanged. Nisoldipine significantly reduced both systolic and diastolic blood pressure when given acutely to elderly hypertensive patients. Major alterations in the pharmacokinetics of nisoldipine were found in 7 patients with chronic liver disease when compared with the elderly hypertensives and healthy volunteers. The values for AUC, Cmax, half-life and volume of distribution were all higher than expected from the volunteer data while clearance was lower. One patient receiving primidone had very low nisoldipine levels, suggesting that the concomitant administration of agents that may induce the metabolism of nisoldipine should be discouraged. Nevertheless, comparisons of nisoldipine plasma levels after acute and chronic administration showed no evidence of any accumulation in either patient population in the doses used. The drug was generally well tolerated although 1 patient with chronic liver disease was withdrawn due to fluid retention.
开展了两项研究，一项针对老年高血压患者，另一项针对慢性肝病患者，以研究年龄和肝病对二氢吡啶类钙拮抗剂尼索地平药代动力学的影响。在17名老年高血压患者中研究了急性和慢性给予尼索地平（每日一次和每日两次）的效果。与之前发表的年轻健康志愿者的数据相比，老年高血压患者的Cmax和AUC值似乎更高，而Tmax和半衰期未变。急性给予老年高血压患者尼索地平时，其显著降低了收缩压和舒张压。与老年高血压患者和健康志愿者相比，7名慢性肝病患者的尼索地平药代动力学有重大改变。AUC、Cmax、半衰期和分布容积的值均高于志愿者数据预期，而清除率较低。一名接受扑米酮治疗的患者尼索地平水平非常低，这表明应避免同时使用可能诱导尼索地平代谢的药物。然而，急性和慢性给药后尼索地平血浆水平的比较显示，在所使用的剂量下，两组患者均无任何蓄积迹象。该药物总体耐受性良好，尽管有1名慢性肝病患者因液体潴留而退出研究。
