Chandler M H, Schran H F, Cutler R E, Smith A J, Gonasun L M, Blouin R A
Drug Product Evaluation Unit, University of Kentucky Medical Center, Lexington.
J Clin Pharmacol. 1988 Dec;28(12):1076-80. doi: 10.1002/j.1552-4604.1988.tb05717.x.
The effect of renal function on isradipine kinetics was examined in four groups of subjects (N = 55) who had normal or impaired renal function. Each subject received isradipine orally as a 10-mg capsule. Serial blood samples were obtained from 0 to 48 hours postdose and the isradipine plasma concentrations determined by radioimmunoassay. Kinetic parameters, Cmax, lambda 3, t 1/2, AUC, CL'o (oral clearance), and CLo (oral clearance standardized to body weight) were determined. Marked intersubject variability of the pharmacokinetic parameters was observed. No statistically significant differences (P greater than .05) were found for AUC, Cl'o, and Clo parameters when renal impairment groups were compared with controls. AUC values were lower (P less than .05), however, for the group with severe renal function impairment than for groups with mild or moderate renal function impairment. No significant correlations (r = -.23, P greater than .05; and r = .13, P greater than .05, respectively) were found between creatinine clearance (CLCR) and CLo and between age and CLo. Considering the interpatient variability in isradipine disposition and the lack of significant differences in CLo between groups, no clear-cut dosing regimen alterations, based on single-dose data, are warranted in renal impairment.
在四组肾功能正常或受损的受试者（N = 55）中研究了肾功能对伊拉地平药代动力学的影响。每位受试者口服10毫克胶囊的伊拉地平。在给药后0至48小时采集系列血样，并通过放射免疫测定法测定伊拉地平血浆浓度。测定了药代动力学参数Cmax、λ3、t1/2、AUC、CL'o（口服清除率）和CLo（按体重标准化的口服清除率）。观察到药代动力学参数存在明显的个体间差异。将肾功能损害组与对照组比较时，AUC、Cl'o和Clo参数未发现有统计学显著差异（P大于0.05）。然而，重度肾功能损害组的AUC值低于轻度或中度肾功能损害组（P小于0.05）。肌酐清除率（CLCR）与CLo之间以及年龄与CLo之间均未发现显著相关性（r分别为-0.23，P大于0.05；r为0.13，P大于0.05）。考虑到伊拉地平处置的患者间变异性以及各组间CLo无显著差异，基于单剂量数据，肾功能损害患者无需明确改变给药方案。
