Pharmacokinetics of lisinopril (MK521) in healthy young and elderly subjects and in elderly patients with cardiac failure

Abstract

The pharmacokinetics of lisinopril were determined in 6 healthy young, 6 healthy elderly and 6 elderly patients with cardiac failure. Lisinopril (5 mg day-1) was administered for 7 days. Plasma lisinopril concentration was measured at 1, 2, 4, 6, 8 and 24 h on days 1 and 7 of the study. The two elderly groups had higher serum lisinopril concentrations than the healthy young subjects (P less than 0.05). There were no significant differences in any of the areas under the curve (AUC) for lisinopril plasma concentration (over time) between the healthy young and healthy elderly groups. The healthy young patients had AUC values on day 7 lower than elderly patients with cardiac failure (P less than 0.01). Creatinine clearance was correlated with lisinopril clearance (r = 0.63; P = 0.006) and with AUC on day 7 (r = -0.67; P = 0.004). Lisinopril clearance was different in the three groups (P less than 0.05): healthy young patients had the highest and elderly patients with cardiac failure the lowest values. Thus, in the elderly a reduced renal clearance of lisinopril leads to higher and more sustained blood levels. In elderly patients with cardiac failure, renal function should be estimated before lisinopril is prescribed as a reduction in dose may be appropriate.