Elimination kinetics of captopril in patients with renal failure.

Captopril kinetics were determined after a 100-mg oral dose of 14C-captopril in 21 patients with various degrees of renal impairment. Elimination kinetics of captopril were evaluated by model-independent methods. The body clearance (ClB) of captopril decreased steadily with decreasing creatinine clearance (ClCr) from 5.2 ml/min/kg for mild renal failure patients to 1.6 ml/min/kg for hemodialysis patients during an interdialytic period. In patients with mild renal impairment, renal and nonrenal clearances of captopril averaged 2.2 and 3.0 ml/min/kg, respectively, and fell (P less than 0.001) to 0.2 and 1.5 ml/min/kg in patients with severe renal impairment. There were no significant differences in the extent of total cumulative excretion (fecal plus urinary) of radioactivity over a 96- to 120-hr period between the patients with mild, moderate, and severe renal impairment. The 48-hr renal excretion of captopril averaged 29, 21, and 8% of the dose in the mild, moderate, and severe renally impaired groups. In five additional hemodialysis patients, the mean dialyzer clearance of captopril averaged 120 ml/min. Approximately 35% of the dose was recovered in the 4-hr dialysate. Based on the above findings, a reduction in the dose of captopril is necessary in patients with renal failure.