Pharmacokinetics of Captopril in Elderly Healthy Male Volunteers

The pharmacokinetics of captopril were studied in 12 healthy male volunteers aged 65 to 76 years, who each received a single 100-mg oral dose. Blood and urine samples were collected over a 24-hour period, and assayed for unchanged captopril (CAP), S-methylcaptopril (Me-CAP, plasma concentrations from 2 subjects only), and total captopril levels (TOT, a mixture of CAP and its dimer and mixed disulfides with endogenous thiol-containing compounds such as glutathione and cysteine). Mean values for the maximum concentration (Cmax) were 803 and 66.3 ng/mL for CAP and Me-CAP, respectively. Mean time to maximum concentration (tmax) was determined as 1.0, 1.4, and 1.0 for CAP, TOT, and Me-CAP, respectively. Mean areas under the plasma concentration-time curve (AUC) were 1,394 hr-ng/mL (CAP, 0-8 hr) and 17,316 hr-ng/mL (TOT, 0-24 hr). The mean estimated half-life (t 1/2) for CAP was 1.4 hr, and its renal clearance was 187 mL/hr/kg. Mean urinary excretion over 24 hr was 20.8 and 53.1 for CAP and TOT, respectively. Cmax, and AUC for CAP were 9% less and 13% greater, respectively, than in a historical control group of 18-35-year-old men, treated in the same clinic, by the same personnel, using the same analytic procedures, whereas the 24-hour urinary excretion was 25% lower and eight-hour renal clearance 36% lower in the older population. Since the values for Cmax, AUC, and t 1/2 were similar in the two populations, it does not appear that the pharmacokinetics of CAP are altered markedly with age alone.