The effects of renal function on the disposition of isradipine

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.