Pharmacokinetics of lisinopril (IV/PO) in healthy volunteers

When three intravenous doses of lisinopril were administered to healthy volunteers, area under the curve (to infinity) vs dose was linear with a positive intercept. Subtracting area under the extrapolated terminal phase of the serum profile from zero to infinity retained the linear relationship, but shifted the regression line to a zero intercept. It is postulated that the terminal phase reflects binding of drug to angiotensin‐converting enzyme (ACE). The half‐life for the terminal phase (approximately 40 h) was not predictive of steadystate parameters when ten daily doses (q24h) of lisinopril were administered orally to healthy volunteers. The mean effective half‐life for accumulation was 12·6h. The mean accumulation ratio was 1·38. Steady state was attained after the second daily dose. The observations in these studies with lisinopril are similar to those reported for enalaprilat, the active metabolite of the ACE inhibitor, enalapril maleate.