Three new long-acting converting-enzyme inhibitors: Relationship between plasma converting-enzyme activity and response to angiotensin I

Biollaz, J.; Burnier, Michel; Turini, G. A.; Brunner, D. B.; Porchet, M; Gómez, Héctor W.; Jones, Keith; Ferber, F; Abrams, William B.; Gavras, Haralambos; Brunner, Hans R.

doi:10.1038/clpt.1981.92

Cited by 145 publications

(45 citation statements)

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“…Lisinopril, the lysine derivative of enalaprilic acid, is a new potent orally active inhibitor of angiotensin converting enzyme (Biollaz et al, 1981). Unlike captopril which is not chemically stable in vivo, (Drummer et al, 1983), or enalapril, which is a prodrug (Larmour et al, 1985), lisinopril does not undergo metabolism in vivo and is thought to be mainly excreted intact by the kidneys (Ulm et al, 1982).…”

Section: Introduction Methodsmentioning

confidence: 99%

Lisinopril pharmacokinetics in chronic renal failure.

Jackson

Cubela

Conway

et al. 1988

Brit J Clinical Pharma

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1 Lisinopril, a new orally active angiotensin converting enzyme inhibitor, was given to eight patients with stable chronic renal failure, in a dose of 5 mg 24 h-1 for 1 week.Creatinine clearance of the subjects ranged from 0.22 to 1.11 ml s 1 Lisinopril pharmacokinetics were studied over 8 days. 2 There was a close correlation between creatinine clearance and total 'area under the curve' over the 8 days of study (r = -0.88, P < 0.05), and plateau lisinopril concentration and creatinine clearance (r = -0.77, P < 0.05). 3 Serum angiotensin converting enzyme activity was inhibited in proportion to log serum lisinopril concentration (r = -0.99, P < 0.001). Calculated IC50 was 47 ng lisinopril ml-1 from pooled data, with individual patients IC50 ranging from 20 to 70 ng lisinopril ml-'. 4 Creatinine clearance was unaltered by treatment. Serum potassium rose to over 5 mmol 1-1 in four patients, without adverse clinical effect.

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Section: Introduction Methodsmentioning

confidence: 99%

Lisinopril pharmacokinetics in chronic renal failure.

Jackson

Cubela

Conway

et al. 1988

Brit J Clinical Pharma

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“…An AII/AI ratio of Ͻ0.05 indicates complete inhibition of the vascular convert-ing enzyme. 6 Pressor response to AI and AII was measured 3 hours after administration of ACE inhibitor. 7…”

Section: Assessment Of Vascular Ace Inhibitionmentioning

confidence: 99%

Elevated Plasma Aldosterone Levels Despite Complete Inhibition of the Vascular Angiotensin-Converting Enzyme in Chronic Heart Failure

et al. 2002

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Background-Plasma aldosterone levels are elevated in patients with chronic heart failure (CHF) taking angiotensinconverting enzyme (ACE) inhibitors. Elevated aldosterone levels may reflect incomplete inhibition of the vascular converting enzyme during long-term ACE inhibition. We simultaneously measured plasma aldosterone levels and the degree of inhibition of the vascular converting enzyme in patients with CHF. Methods and Results-Thirty-four subjects with CHF receiving the maximum recommended doses of ACE inhibitors for a duration of 3 to 105 months were studied. The pressor response to exogenous angiotensin I (AI) was measured and normalized for the pressor response to angiotensin II (AII) to assess inhibition of the vascular converting enzyme (AII/AI ratio). Aldosterone levels were determined by solid-phase radioimmunoassay. Eleven of the 34 subjects had plasma aldosterone levels above the upper limit of normal, ie, Ͼ15.0 ng/dL. Seven of these 11 subjects (64%) had an AII/AI ratio Յ0.05, indicating complete inhibition of the vascular converting enzyme. In the entire cohort, the AII/AI ratio did not correlate with the duration of ACE inhibitor therapy. Conclusions-Plasma aldosterone levels are elevated in patients with CHF during long-term ACE inhibitor therapy despite complete inhibition of the vascular converting enzyme. Complete inhibition of the vascular converting enzyme does not obviate the need for aldosterone receptor blockade in patients with CHF.

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“…1 Because plasma renin activity (PRA) is increased in heart failure and angiotensin II (AngII) is a potent stimulator of vasoconstriction, aldosterone release, and cardiovascular cellular growth, the hemodynamic benefit and mortality reduction from these drugs have been attributed to a reduction of AngII levels. [2][3][4] Controversy has nonetheless arisen regarding the ability of ACE inhibitors to produce long-term suppression of AngII levels.…”

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confidence: 99%

Augmented Short- and Long-Term Hemodynamic and Hormonal Effects of an Angiotensin Receptor Blocker Added to Angiotensin Converting Enzyme Inhibitor Therapy in Patients With Heart Failure

et al. 1999

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for the Vasodilator Heart Failure Trial (V-HeFT) Study Group* Background-ACE inhibitors may not adequately suppress deleterious levels of angiotensin II in patients with heartfailure. An angiotensin receptor blocker added to an ACE inhibitor may exert additional beneficial effects. Methods and Results-Eighty-three symptomatic stable patients with chronic heart failure receiving long-term ACE inhibitor therapy were randomly assigned to double-blind treatment with valsartan 80 mg BID, valsartan 160 mg BID, or placebo while receiving their usual ACE inhibitor therapy. Studies were performed before and after the first dose of the test drug and again after 4 weeks of therapy. A single dose of lisinopril was administered during study days to ensure sustained ACE inhibition. Compared with placebo, the first dose of valsartan 160 mg resulted in a significantly greater reduction in pulmonary capillary wedge pressure at 3, 4, and 8 hours and during the prespecified 4-to 8-hour interval after the dose and in systolic blood pressure at 2, 3, 6, 8, and 12 hours and 4 to 8 hours after the dose. A pressure reduction from valsartan 80 mg did not achieve statistical significance. After 4 weeks of therapy, net reductions in 0-hour trough pulmonary capillary wedge pressure (Ϫ4.3 mm Hg; Pϭ0.16), pulmonary artery diastolic pressure (Ϫ4.7 mm Hg; Pϭ0.013), and systolic blood pressure (Ϫ6.8 mm Hg; Pϭ0.013) were observed in the valsartan 160 mg group compared with placebo. After 4 weeks of therapy, plasma aldosterone was reduced by valsartan 80 mg BID (Ϫ52.1 pg/mL; Pϭ0.001) and 160 mg BID (Ϫ47.8 pg/mL; PϽ0.001) compared with placebo, and there was a trend for a reduction in plasma norepinephrine (Ϫ97 pg/mL; Pϭ0.10). Seventy-four of the 83 patients completed the trial. Conclusions-Physiologically active levels of angiotensin II persist during standard long-term ACE inhibitor therapy.

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Three new long-acting converting-enzyme inhibitors: Relationship between plasma converting-enzyme activity and response to angiotensin I

Cited by 145 publications

References 0 publications

Lisinopril pharmacokinetics in chronic renal failure.

Lisinopril pharmacokinetics in chronic renal failure.

Elevated Plasma Aldosterone Levels Despite Complete Inhibition of the Vascular Angiotensin-Converting Enzyme in Chronic Heart Failure

Augmented Short- and Long-Term Hemodynamic and Hormonal Effects of an Angiotensin Receptor Blocker Added to Angiotensin Converting Enzyme Inhibitor Therapy in Patients With Heart Failure

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