Pharmacokinetics of enalapril in normal subjects and patients with renal impairment.

Kelly, J.G.; Doyle, Gerald D.; Donohue, John A.; Laher, M; Vandenburg, M. J.; Wj, Currie; Cooper, WD

doi:10.1111/j.1365-2125.1986.tb02823.x

Cited by 53 publications

(26 citation statements)

References 5 publications

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“…The influence of renal insufficiency on the serum profiles of enalapril and enalaprilat has also been investigated (Kelly et al, 1986;Lowenthal et al, 1985). Decreased renal function is associated with increased serum concentration of enalaprilat, increased time to peak concentration, slower decline in serum concentrations and with decreased urinary elimination of the drug (Kelly et al, 1986;Lowenthal et al, 1985). This results in decreased dosage requirements of enalapril maleate.…”

Section: Pharmacokinetic Parametersmentioning

confidence: 99%

Pharmacokinetics of cilazapril in patients with renal failure.

Fillastre

Moulin

Godin

et al. 1989

Brit J Clinical Pharma

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1. The pharmacokinetics of a single 1 mg dose of cilazapril were determined in six subjects with normal renal function and in 19 uraemic patients with various degrees of renal impairment. 2. Significant decreases in systolic and diastolic blood pressure were noted in all groups of subjects between 2 and 8 h after administration of 1 mg cilazapril. 3. There was a significant correlation between ACE inhibition at 24 h and creatinine clearance (CrCL). 4. For cilazapril, Cmax and tmax were independent of creatinine clearance. AUC(24) was inversely related to CrCL and apparent plasma clearance (CL/F) was directly related to CrCL. 5. For cilazaprilat, Cmax and tmax were related to creatinine clearance. AUC(24) was inversely related to CrCl and apparent plasma clearance (CL/F) was directly related to CrCL. 6. Dialysis clearance was approximately 2 l h‐1 for cilazapril and for cilazaprilat. 7. The effects of renal impairment on cilazapril and cilazaprilat kinetics were similar to those observed for other inhibitors of angiotensin‐converting enzyme such as captopril, enalapril and lisinopril. 8. It may be necessary to modify doses of cilazapril for the treatment of essential hypertension in uraemic patients. When creatinine clearance was below 15 ml min‐1 cilazaprilat concentrations were increased, half‐lives were prolonged and ACE inhibition remained above 90% for at least 24 h. A reduced dosage is indicated for these patients. 9. In patients requiring haemodialysis, maintenance doses of 0.5 mg given after each haemodialysis session are sufficient.

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Section: Pharmacokinetic Parametersmentioning

confidence: 99%

Pharmacokinetics of cilazapril in patients with renal failure.

Fillastre

Moulin

Godin

et al. 1989

Brit J Clinical Pharma

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“…Many other ACE inhibitors, either directly acting compounds such as captopril (Giudicelli et al, 1984) and lisinopril (Jackson et al, 1988) or active metabolites of prodrugs such as enalaprilat (Kelly et al, 1986;Lowenthal et al, 1985), ramiprilat (Aurell et al, 1987;Debusmann et al, 1987), cilazaprilat (Shionoiri et al, 1988), alaceprilat (Onoyama et al, 1986) and pentoprilat (Rakhit et al, 1988), as well as the active metabolites of delapril (Onoyama et al, 1988) are mainly cleared by the kidney. Thus, impaired renal function results in higher circulating concentrations of the active drugs, and increased extent and duration of ACE inhibition.…”

Section: Discussionmentioning

confidence: 99%

The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure.

Sennesael

Ali

Sweny

et al. 1992

Brit J Clinical Pharma

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“…In renal dysfunction, the clearance of renally-excreted ACE inhibitors is compromised, resulting in undesirable elevation of plasma levels (Kelly et al, 1986;van Schaik et al, 1987), supra-optimal inhibition of ACE and increased potential for adverse reactions. Hence the need for careful monitoring when these compounds are used and, usually, some reduction in dosage or dose interval in patients whose renal function is impaired.…”

Section: Discussionmentioning

confidence: 99%

“…There have been a number of studies (e.g. Kelly et al, 1986;van Schaik et al, 1987;Shionoiri et al, 1987) showing that plasma levels of ACE inhibitors in current clinical use are elevated in patients with renal impairment, necessitating closer monitoring and possible dose reduction. Thus, renal excretion of ACE inhibitors is potentially disadvantageous.…”

Section: Introductionmentioning

confidence: 99%

Preferential biliary elimination of FPL 63547, a novel inhibitor of angiotensin‐converting enzyme, in the rat

Carr¹,

Cooper²,

Hutchinson³

et al. 1990

British J Pharmacology

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1The route of elimination of FPL 63547, a novel inhibitor of angiotensin-converting enzyme (ACE), has been investigated in the anaesthetized rat. Comparisons have been made with other ACE inhibitors. 2 Bile and urine samples were collected over a 5 hour period following a single i.v. dose of ACE inhibitor (2 ymol kg'-). Samples were bioassayed for ACE inhibitory activity using affinity-purified rabbit lung ACE and the amounts of the active form of inhibitor present in each sample were calculated by comparison with a standard curve. 3 FPL 63547 was rapidly and extensively excreted as the diacid in the bile but appeared in the urine in negligible amounts. The bile:urine ratio was 21.4:1 indicating a marked preference for the biliary route. A similar elimination profile was observed when the compound was dosed in its active form (FPL 63547 diacid), 87.9% of which was found in the bile over the 5 h collection period, with a bile: urine ratio of 14.6:1. 4 The marked preference of FPL 63547 for biliary elimination was not shared by the other ACE inhibitors tested in this study. Lisinopril demonstrated the opposite pattern, being excreted almost exclusively by the kidney (bile:urine ratio 0.06:1). Enalapril was eliminated in approximately equal amounts in bile and urine (ratio 0.7:1) while spirapril diacid showed a slight preference for the bile (ratio 2.6:1).5

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Pharmacokinetics of enalapril in normal subjects and patients with renal impairment.

Cited by 53 publications

References 5 publications

Pharmacokinetics of cilazapril in patients with renal failure.

Pharmacokinetics of cilazapril in patients with renal failure.

The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure.

Preferential biliary elimination of FPL 63547, a novel inhibitor of angiotensin‐converting enzyme, in the rat

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