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

Gautam, P C; Vargas, Enrique; Lye, Michael

doi:10.1111/j.2042-7158.1987.tb03130.x

Cited by 39 publications

(23 citation statements)

References 5 publications

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“…Similar pharmacokinetic results have been obtained from volunteer studies of other ACE inhibitors such as captopril (Creasey et al, 1986), enalapril (Hockings et al, 1986), lisinopril (Gautam et al, 1987), ramipril (Meyer et al, 1987), and pentopril (Rakhit et al, 1987). Pharmacodynamic and therapeutic studies in hypertensive patients may suggest the use of reduced dosages of ACE inhibitors in the elderly.…”

Section: Discussionsupporting

confidence: 69%

A pharmacokinetic study of cilazapril in elderly and young volunteers.

Williams¹,

Brown²,

Rajaguru³

et al. 1989

Brit J Clinical Pharma

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1 Cilazaprilat is an inhibitor of angiotensin converting enzyme (ACE) and is the active metabolite of cilazapril. The pharmacokinetics of cilazaprilat, and the inhibition of plasma ACE were investigated in 12 elderly and 12 young healthy volunteers. 2 Single oral 1 mg doses of cilazapril were given to the elderly (age range 65-83 years) and the young (age range 18-31 years) in an open study. Plasma and urinary cilazaprilat concentrations, and plasma ACE activities were measured up to 72 h after dosing by radioenzymatic methods. 3 Cilazapril was well tolerated in both young and elderly subjects. Small falls in blood pressure were observed up to 8-24 h after dosing.4 The mean peak plasma cilazaprilat concentration in the elderly (11.5 ng ml-') was significantly greater (P < 0.02) than the corresponding value in the young (8.3 ng ml-').Total and renal clearances were significantly lower (both P < 0.05) in the elderly (12.8 and 5.1 1 h-1) than in the young (16.0 and 7.21 h-1). Total urinary recovery of cilazaprilat was similar for the two groups at about 43% of dose. 5 Plasma ACE inhibition was slightly greater in the elderly but the mean inhibition in the two groups did not differ by more than 10% at any time-point from 1-72 h. 6 The plasma concentrations of cilazaprilat required for 90% ACE inhibition were similar at 4.7 and 4.8 ng ml-1 in the elderly and young respectively. 7 It is concluded that the age-related changes in cilazaprilat kinetics and in the degree of ACE inhibition are small. On their own, these changes do not imply a need for reduced dosage in the elderly but further clinical experience will help to establish a suitable dosage regimen of cilazapril for elderly hypertensives.

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Section: Discussionsupporting

confidence: 69%

A pharmacokinetic study of cilazapril in elderly and young volunteers.

Williams¹,

Brown²,

Rajaguru³

et al. 1989

Brit J Clinical Pharma

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“…Using a population pharmacokinetic approach, Thompson et al [8] reported that the clearance of lisinopril was reduced in patients with CHF in association with a reduction in renal function. Gautam et al [9] reported similar findings and proposed that lisinopril dosage should be adjusted on the basis of renal function in elderly patients with CHF. Differences in ramipril pharmacokinetics between patients with CHF and normal subjects may also be attributable to reduced renal function in elderly patients with CHF [10].…”

Section: Discussionsupporting

confidence: 55%

The pharmacokinetics of quinapril and quinaprilat in patients with congestive heart failure.

Begg

Robson

Ikram

et al. 1994

Brit J Clinical Pharma

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The pharmacokinetics of quinapril and its active metabolite quinaprilat were studied in 12 patients with congestive heart failure (CHF) after multiple oral doses of 10 mg quinapril twice daily. Six patients had an ejection fraction of <35% and six had an ejection fraction between 35%-50%. Increases in the apparent elimination half-life and in AUC(O, 1 2h) values of quinaprilat were associated with smaller ejection fractions, decreased creatinine clearance, and increased patient age. Comparison with data from age-matched controls having comparable renal function suggests that creatinine clearance is the major determinant of quinaprilat clearance. CHF per se appears to have minimal effect. Dosing of quinapril in patients with CHF should be based on their renal function.

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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: 97%

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

Cited by 39 publications

References 5 publications

A pharmacokinetic study of cilazapril in elderly and young volunteers.

A pharmacokinetic study of cilazapril in elderly and young volunteers.

The pharmacokinetics of quinapril and quinaprilat in patients with congestive heart failure.

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

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