Pharmacokinetics of lisinopril (IV/PO) in healthy volunteers

Abstract

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 steady-state parameters when ten daily doses (q24h) of lisinopril were administered orally to healthy volunteers. The mean effective half-life for accumulation was 12.6 h. 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.

A multicenter study of the pharmacokinetics of lisinopril in pediatric patients with hypertension

“…In a previous study in which eight healthy adults were given daily doses of 20 mg lisinopril for 10 days, the mean AUC 0-24 h was 493.5 ng·h/mL, and the mean AUC 0-24 h per 1.0 mg/m 2 was 93.3 ng·h/mL. The mean daily dose in adults in this previous study (adjusted to simulate a 10-mg dose) was 0.14 mg/kg; the mean C max was 82 ng/mL [23]. If this number is divided by 2 to simulate a 10-mg dose, the resulting mean C max is 41 ng/mL; the mean C max per 0.15 mg/kg was 43.5 ng/mL, and mean C max per 1.0 mg/m 2 was 7.8 ng/mL.…”

Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure

“…The profiles of serum concentrationtime curves are similar to saturation curves indicating that the first portion of the absorbed substance may accumulate in a blood compartment which is not notably involved in elimination processes. In previous investigations Beermann et al [23,24] suggested that this compartment may be equivalent with binding to serum ACE (about 3 mol. kl).…”

The pharmacokinetics of lisinopril in hospitalized patients with congestive heart failure.

“…The results of a study in which a single 10 mg oral dose of lisinopril was given to normal subjects (Ulm et al, 1982) and a study in which a 5 mg dose of lisinopril was given as an intravenous bolus in normal subjects (Beermann et al, 1986(Beermann et al, , 1988 serve as a basis of comparison for the results obtained in this study in patients with congestive heart failure (CHF), although statistical comparisons across studies are not appropriate. Essentially all of the dose is recovered in the urine when lisinopril is administered intravenously to normal subjects and patients with congestive heart failure.…”

“…Given the observed increase in AUC for intravenously '.7: Figure 3 Mean serum concentrations of lisinopril following a 10 mg oral dose in normal subjects (Ulm et al, 1982) (o) and in patients with congestive heart failure (e) (n = 12). As with enalaprilat (Till et al, , 1984 it has been postulated that the terminal phase of the lisinopril serum concentration profile reflects nonlinear binding of lisinopril to angiotensin converting enzyme (Beermann et al, 1986). The contribution of a nonlinear binding component to lisinopril serum profiles precludes conventional model-dependent and model-independent calculations of such parameters as apparent volume of distribution, clearance and serum half-life unless the serum data can be appropriately corrected for this binding.…”