Comparison of the angiotensin II antagonist UP269-6 with the angiotensin converting enzyme inhibitor enalapril in normotensive volunteers challenged with angiotensin I

Détails

ID Serval
serval:BIB_06D0867C0CE6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Comparison of the angiotensin II antagonist UP269-6 with the angiotensin converting enzyme inhibitor enalapril in normotensive volunteers challenged with angiotensin I
Périodique
Journal of Cardiovascular Pharmacology
Auteur(s)
Inglessis  N., Nussberger  J., Hagmann  M., Hiesse-Provost  O., Insuasty  J., Reid  J., Menard  J., Brunner  H. R.
ISSN
0160-2446 (Print)
Statut éditorial
Publié
Date de publication
06/1995
Volume
25
Numéro
6
Pages
986-93
Notes
Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial --- Old month value: Jun
Résumé
We assessed the inhibitory effect of UP269-6, a new orally active angiotensin II (ANG II) receptor antagonist, on the pressor action of exogenous ANG I in healthy male volunteers maintained on an unrestricted sodium intake and compared it with that of enalapril. Seven different single doses of UP269-6 ranging from 5 to 180 mg, 20 mg enalapril, or placebo were administered to 16 subjects in a double-blind fashion. The order of placebo and enalapril was randomized, and UP269-6 was given in an ascending dose order. The peak systolic blood pressure (SBP) response to a test dose of ANG I was determined serially before and after oral drug administration by monitoring finger BP by a photoplethysmographic method. No drug-related side effect was observed. There was a dose-dependent inhibition of the SBP response to the ANG I challenge. Doses as low as 40 to 80 mg had blocking effects quite similar to that of enalapril 20 mg. Ten hours after the 20- and 40-mg doses of UP269-6, the SBP response was still attenuated when drug levels no longer were measurable in plasma. UP269-6 also produced a dose-related increase in active renin and ANG II levels at 24 h after drug intake. In these volunteers on unrestricted salt intake, no statistically significant effect on 24-h urinary aldosterone excretion was observed. Based on these preliminary data, the pharmacokinetic drug half-life (t 1/2) was estimated at 4.7 h and the EC50 was estimated at 41 ng/ml. UP269-6 appears to be a well-tolerated, potent, orally active, antagonist of ANG II receptors in men. Doses of 40-80 mg might block the ANG I pressor response as does enalapril 20 mg.
Mots-clé
Administration, Oral Adult Aldosterone/urine Analysis of Variance Angiotensin I/administration & dosage/*adverse effects Angiotensin II/blood Angiotensin-Converting Enzyme Inhibitors/administration & dosage/pharmacokinetics/*pharmacology Blood Pressure/*drug effects Blood Pressure Determination Dose-Response Relationship, Drug Double-Blind Method Enalapril/administration & dosage/pharmacokinetics/*pharmacology Humans Male Plethysmography Pyrimidines/administration & dosage/pharmacokinetics/*pharmacology Receptors, Angiotensin/*antagonists & inhibitors Renin/blood Tetrazoles/administration & dosage/pharmacokinetics/*pharmacology
Pubmed
Web of science
Création de la notice
05/03/2008 16:39
Dernière modification de la notice
20/08/2019 12:29
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