Effects of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase on the vasopressor response to exogenous angiotensin I and angiotensin II challenges in healthy volunteers.

Détails

ID Serval
serval:BIB_3E9FAC34D6E6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Effects of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase on the vasopressor response to exogenous angiotensin I and angiotensin II challenges in healthy volunteers.
Périodique
Journal of Cardiovascular Pharmacology
Auteur(s)
Rousso P., Buclin T., Nussberger J., Brunner-Ferber F., Brunner H.R., Biollaz J.
ISSN
0160-2446 (Print)
ISSN-L
0160-2446
Statut éditorial
Publié
Date de publication
1998
Peer-reviewed
Oui
Volume
31
Numéro
3
Pages
408-417
Langue
anglais
Notes
Publication types: Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
MDL 100,240, a dual inhibitor of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), was administered intravenously to two panels of four healthy males in a four-period, dose-increasing (0, 1.56, 6.25, and 25 mg, and 0, 3.13, 12.5, and 50 mg, respectively) double-blind, placebo-controlled study. Plasma ACE activity and blood-pressure response to exogenous angiotensin I and angiotensin II i.v. challenges and safety and tolerance were assessed over a 24-h period. MDL 100,240 induced a rapid, dose-related, and sustained inhibition of ACE (>70% over 24 h at doses > or =12.5 mg). The time integral of ACE inhibition was related to the dose but with near-maximal values already attained at doses > or =12.5 mg. Systolic and diastolic blood-pressure responses to exogenous angiotensin I challenges were inhibited in a dose-dependent fashion, whereas the effects of angiotensin II remained unaffected. Mean supine blood pressure decreased transiently (3 h) at doses > or =3.125 mg and < or =24 h with the 25- and 50-mg doses, but not significantly. MDL 100,240 was well tolerated. In healthy subjects, MDL 100,240 exerts a dose-dependent and long-lasting ACE-blocking activity, also expressed by the inhibition of the pressor responses to exogenous angiotensin I challenges. The baroreceptor reflex, assessed by the response to exogenous angiotensin II challenge, remains unaltered.
Mots-clé
Adult, Angiotensin I/administration & dosage, Angiotensin II/administration & dosage, Angiotensin-Converting Enzyme Inhibitors/pharmacokinetics, Angiotensin-Converting Enzyme Inhibitors/pharmacology, Antihypertensive Agents/pharmacokinetics, Antihypertensive Agents/pharmacology, Area Under Curve, Benzazepines/pharmacokinetics, Benzazepines/pharmacology, Blood Pressure/drug effects, Double-Blind Method, Enzyme Inhibitors/pharmacokinetics, Enzyme Inhibitors/pharmacology, Humans, Male, Neprilysin/antagonists & inhibitors, Placebos, Pyridines/pharmacokinetics, Pyridines/pharmacology, Reference Values
Pubmed
Web of science
Création de la notice
05/03/2008 16:41
Dernière modification de la notice
20/08/2019 13:35
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