Pharmacokinetics and Antihypertensive Effects of Lisinopril in Hypertensive Patients with Normal and Impaired Renal Function

Shionoiri, Hiroshi; Minamisawa, Kohsuke; Ueda, Shinichiro; Abe, Yasuhiko; Ebina, Toshiaki; Sugimoto, Koh‐ichi; Matsukawa, Tetsuya; Gotoh, Eiji; Ishii, Masao

doi:10.1097/00005344-199010000-00010

Cited by 17 publications

(11 citation statements)

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“…After chronic administration ACE activity was almost completely inhibited both in volunteers and in patients. A similar (complete) inhibition of ACE activity in patients with chronic renal failure was documented in a study of Shionori et al [26] after chronic therapy with a standard dose of 10 mg lisinopril. Ninety-six hours after the last drug intake mean serum ACE activity in our patients was below the corresponding value found in the volunteers.…”

Section: Discussionsupporting

confidence: 72%

Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure

Neubeck

Fliser²,

Pritsch³

et al. 1994

Eur J Clin Pharmacol

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To prevent drug accumulation and adverse effects the dose of hydrophilic angiotensin-converting enzyme (ACE) inhibitors, e.g. lisinopril, must be reduced in patients with renal failure. To obtain a rational basis for dose recommendations, we undertook a prospective clinical trial. After 15 days of lisinopril treatment pharmacokinetic and pharmacodynamic parameters were determined in patients with advanced renal failure (n = 8; endogenous creatinine clearance [CLCR]: 18 ml.min-1.1.73 m-2) and in healthy subjects with normal renal function (n = 16; CLCR: 107 ml.min-1.1.73 m-2). The volunteers received 10 mg lisinopril once daily, the daily dose in patients (1.1-2.2 mg) was adjusted to the individual CLCR according to the method of Dettli [13]. After 15 days of lisinopril treatment the mean maximal serum concentration (Cmax) in patients was lower than in volunteers (30.7 vs 40.7 ng.ml-1, while the mean area under the concentration-time curve (AUC0-24 h) was higher (525 vs 473 ng.h-1.ml-1). ACE activity on day 15 was almost completely inhibited in both groups. Plasma renin activity, angiotensin I and angiotensin II levels documented marked inhibition of converting enzyme in volunteers and patients. Furthermore, average mean arterial blood pressure in patients decreased by 5 mmHg and proteinuria from 3.9-2.7 g per 24 h after 15 days of treatment with the reduced dose of lisinopril. Adjustment of the dose of lisinopril prevents significant accumulation of the drug in patients with advanced renal failure during chronic therapy. Mean serum levels did not exceed this in subjects with normal renal function receiving a standard dose.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 72%

Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure

Neubeck

Fliser²,

Pritsch³

et al. 1994

Eur J Clin Pharmacol

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“…In contrast, Johnston & Duffin [20] documented no alterations in lisinopril pharmacokinetics in patients with CHF. Shionoiri et al [7], Kelly et al [21] and van Schaik et al [22] noted reduced clearance and increased plasma concentrations of lisinopril in patients with renal dysfunction. In one study, the effective half‐life of lisinopril doubled and tripled in patients with mild and severe renal impairment, respectively [22].…”

Section: Discussionmentioning

confidence: 99%

“…Although a number of angiotensin converting enzyme (ACE) inhibitors are effective in CHF [3–5], their utility may differ, especially in the face of concomitant renal impairment. For example, the elimination of lisinopril and enalapril is significantly decreased in patients with either CHF or renal impairment [6–8], and reduced doses for both drugs have been advocated to avoid adverse events [6, 7, 9].…”

Section: Introductionmentioning

confidence: 99%

Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency

Greenbaum

Zucchelli

Caspi

et al. 2000

Brit J Clinical Pharma

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Aims To compare the serum pharmacokinetics of fosinoprilat with enalaprilat and lisinopril after 1 and 10 days of dosing with fosinopril, enalapril and lisinopril. Methods Patients with congestive heart failure (CHF, NYHA Class II–IV) and chronic renal insufficiency (creatinine clearance ≤30 ml min−1 ) were randomized to receive fosinopril, enalapril or lisinopril in two parallel‐group studies. In the first study 24 patients were treated with 10 mg fosinopril (n=12 patients) or 2.5 mg enalapril (n=12) every morning for 10 consecutive days. In the second study 31 patients were treated with 10 mg fosinopril (n=16 patients) or 5 mg lisinopril (n=15) every morning for 10 consecutive days. Samples of blood were collected for determination of pharmacokinetic parameters. The area under the curve (AUC) between the first and last days of treatment and the accumulation index (AI) were the primary outcome measures. Results All three angiotensin converting enzyme (ACE) inhibitors exhibited a significant increase in AUC between the first and last days of treatment in both studies. The difference between the AI for fosinoprilat (1.41) and enalaprilat (1.96) was statistically significant (95% CI: 1.05, 1.84). Similarly, the difference between the AI for fosinoprilat (1.21) and lisinopril (2.76) was statistically significant (95% CI: 1.85, 2.69). All three ACE inhibitors completely inhibited serum ACE for 24 h. All treatments were well tolerated. Conclusions Fosinoprilat exhibits significantly less accumulation than enalaprilat or lisinopril in patients with CHF and renal insufficiency, most probably because fosinoprilat is eliminated by both the kidney and liver, and increased hepatic elimination can compensate for reduced renal clearance in patients with kidney dysfunction.

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“…However, excretion of several ACE inhibitors, including lisinopril and enalaprilat (the active diacid metabolite of enalapril), depends exclusively on renal clearance. In patients with renal insufficiency, plasma clearance of both lisinopril and enalaprilat decreases and significant accumulation occurs (Fruncillo et al 1987;Gautam et al 1987;Shionoiri et al 1990). It has been suggested that the dosage of enalapril or lisinopril should be decreased as renal function declines, to compensate for the altered pharmacokinetics (Begg et al 1989;Kelly et al 1988).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Steady-State Pharmacokinetics of Fosinopril, Lisinopril and Enalapril in Patients with Chronic Renal Insufficiency

Sica

Cutler

Parmer

et al. 1991

Clinical Pharmacokinetics

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The phosphinyl ester prodrug fosinopril, a new angiotensin converting enzyme (ACE) inhibitor, is fully hydrolysed after oral administration to the pharmacologically active diacid, fosinoprilat. This metabolite is cleared by both hepatic and renal routes, while most other ACE inhibitors are cleared exclusively by the kidney. In the present study, after administration of multiple fixed oral doses the accumulation of the active moieties of fosinopril, enalapril and lisinopril was compared in patients with renal insufficiency. 29 patients with creatinine clearances (CLCR) less than 30 ml/min received either fosinopril 10mg (n = 9), enalapril 2.5mg (n = 10) or lisinopril 5mg (n = 10) once daily for 10 days in a nonblind (open-label) parallel study. Pharmacokinetic parameters including area under the serum concentration-time curve (AUC), peak serum concentration (Cmax) and time to peak concentration (tmax), as well as renal function, blood pressure, and plasma renin activity (PRA) and aldosterone levels, were determined on the first and last days of the study. The percentage (+/- SEM) increases in AUC from day 1 to day 10 for fosinoprilat, enalaprilat and lisinopril were 26.8 +/- 9.9 (nonsignificant), 76.6 +/- 16.6 (p less than 0.001) and 161.7 +/- 31.8% (p less than 0.001), respectively. These results indicate that there was significantly less accumulation of fosinoprilat, based on accumulation indices, relative to either enalaprilat (p less than 0.05) or lisinopril (p less than 0.001) during the study. The Cmax of fosinopril increased significantly less than that of lisinopril (21.1 vs 123.6%; p less than 0.01). Renal function was not altered in any group, and blood pressure changed modestly.(ABSTRACT TRUNCATED AT 250 WORDS)

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Pharmacokinetics and Antihypertensive Effects of Lisinopril in Hypertensive Patients with Normal and Impaired Renal Function

Cited by 17 publications

References 0 publications

Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure

Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure

Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency

Comparison of the Steady-State Pharmacokinetics of Fosinopril, Lisinopril and Enalapril in Patients with Chronic Renal Insufficiency

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