The effects of renal function on PK of omapatrilat

Malhotra, Bimal; Sica, Domenic A.; Khan, Sanaullah; Delaney, Carol; Ferreira, Irene; Hammett, J.L.; Jemal, M.; Liao, Wei-Chi

doi:10.1016/s0009-9236(99)80067-8

Cited by 4 publications

(2 citation statements)

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“…The plasma concentrations of omapatrilat administered to 29 patients with moderate to severe renal impairment, and even on hemodialysis treatment, did not differ from controls with normal renal function [45]. Therefore, no dose adjustment of omapatrilat will be required in patients with renal impairment, independent of its severity.…”

Section: Vasopeptidase Inhibitors and The Kidneymentioning

confidence: 91%

“…Furthermore, in a study of 690 patients with mild to moderate hypertension, omapatrilat (5-40 mg/d) lowered systolic blood pressure to a significantly greater extent than lisinopril (20-40 mg/d) [42]. In patients with renal impairment, there was no need for dose reduction of omapatrilat [43,44], independent of the degree of impaired renal function [45].…”

Section: Vasopeptidase Inhibitors In the Treatment Of Hypertensionmentioning

confidence: 99%

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Vasopeptidase inhibition: Effective blood pressure control for vascular protection

Quaschning

Ruschitzka²,

Lüscher³

2002

Current Science Inc

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Angiotensin converting enzyme (ACE) inhibition is a well-established principle in the treatment of hypertension, and numerous large scale clinical studies have clearly demonstrated the beneficial effects of inhibiting the renin-angiotensin-aldosterone system (RAS) in hypertension. The clinical success of ACE inhibitors encouraged attempts to inhibit other key enzymes in the regulation of vascular tone, such as the neutral endopeptidase (NEP). Similar to ACE, NEP is an endothelial cell surface metalloproteinase, which is involved in the degradation of several regulatory peptides including the natriuretic peptides, and augments vasodilatation and natriuresis through increased levels of atrial natriuretic peptide. By inhibiting the RAS and potentiating the natriuretic peptide system at the same time, combined NEP/ACE inhibitors, the so-called "vasopeptidase inhibitors," reduce vasoconstriction and enhance vasodilatation, and in turn decrease peripheral vascular resistance and blood pressure. Within the vessel wall this may lead to a reduction of vasoconstrictor and proliferative mediators such as angiotensin II and endothelin-1, and may increase local levels of bradykinin as well as natriuretic peptides. Based on these considerations, numerous preclinical studies with vasopeptidase inhibitors have been performed and reveal promising results in experimental hypertension. Correspondingly, large-scale clinical studies in patients with hypertension are on the way, to transfer the principle of vasopeptidase inhibition from bench to bedside.

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Section: Vasopeptidase Inhibitors and The Kidneymentioning

confidence: 91%

Section: Vasopeptidase Inhibitors In the Treatment Of Hypertensionmentioning

confidence: 99%

Vasopeptidase inhibition: Effective blood pressure control for vascular protection

Quaschning

Ruschitzka²,

Lüscher³

2002

Current Science Inc

View full text Add to dashboard Cite

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Vasopeptidase inhibitors

Weber

2001

The Lancet

102

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Vasopeptidase inhibitors are a new class of cardiovascular drug that simultaneously inhibit both neutral endopeptidase and angiotensin-converting enzyme (ACE). They increase the availability of peptides that have vasodilatory and other vascular effects; they also inhibit production of angiotensin II. In animal models vasopeptidase inhibitors decrease blood pressure in low, medium, and high renin forms of hypertension, and they also appear to confer benefits in models of heart failure and ischaemic heart disease. Studies in human hypertension show that these agents are effective in decreasing blood pressure regardless of race or age. Experience with omapatrilat, the most clinically advanced of these drugs, has shown it to be more effective than currently available ACE inhibitors or other widely used antihypertensive agents. Studies with omapatrilat in congestive heart failure have shown beneficial effects on haemodynamics and symptoms. The vasopeptidase inhibitors appear to have safety profiles similar to ACE inhibitors, though the frequency of side-effects such as angio-oedema and cough remains to be established. Large trials with clinical endpoints, some already in progress, are needed to establish the place of this class of drug beside that of established therapies in conditions such as hypertension, heart failure, ischaemic heart disease, and nephropathy.

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Vasopeptidase inhibition: A new treatment approach for endothelial dysfunction

Quaschning

Galle

Wanner

2003

Kidney International

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Angiotensin-converting enzyme (ACE) inhibition is a well-established principle in the treatment of endothelial dysfunction. Numerous preclinical and clinical studies have clearly demonstrated the beneficial effects of inhibiting the renin-angiotensin-aldosterone system (RAS) in states of impaired endothelial function. The successful use of ACE inhibitors encouraged attempts to inhibit other key enzymes in the regulation of vascular tone, such as the neutral endopeptidase (NEP). Similar to ACE, NEP is an endothelial cell surface metalloproteinase that is involved in the degradation of several regulatory peptides, including the natriuretic peptides, and, thus, NEP inhibition augments vasodilatation and natriuresis through increased levels of atrial natriuretic peptide (ANP). By inhibiting the RAS and potentiating the natriuretic peptide system at the same time, combined NEP/ACE inhibitors, the so-called vasopeptidase inhibitors, reduce vasoconstriction and enhance vasodilatation, thereby decreasing peripheral vascular resistance and blood pressure. Within the vessel wall this may lead to a reduction of vasoconstrictor and proliferative mediators, such as angiotensin II and endothelin-1, and may increase local levels of bradykinin as well as natriuretic peptides. Even though first results of both preclinical and clinical studies indicate that combined inhibition of ACE and NEP by vasopeptidase inhibitors represents a promising strategy in the treatment of hypertension and heart failure, angioedema occurs more frequently on vasopeptidase inhibition as compared to ACE inhibition. To establish vasopeptidase inhibition as a novel option in the treatment of cardiovascular disease, further validation of efficacy and safety of this promising therapeutic principle is mandatory.

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The effects of renal function on PK of omapatrilat

Abstract: Clinical Pharmacology & Therapeutics (1999) 65, 134–134; doi:

Cited by 4 publications

References 0 publications

Vasopeptidase inhibition: Effective blood pressure control for vascular protection

Vasopeptidase inhibition: Effective blood pressure control for vascular protection

Vasopeptidase inhibitors

Vasopeptidase inhibition: A new treatment approach for endothelial dysfunction

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