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

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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 < 0ṁ05). 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 < 0ṁ01). Creatinine clearance was correlated wth lisinopril clearance (r = 0ṁ63; P = 0ṁ006) and with AUC on day 7 (r = −0ṁ67; P = 0ṁ004). Lisinopril clearance was different in the three groups (P < 0ṁ05): 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.