Hemodynamic and humoral effects of the new renin inhibitor enalkiren in normal humans.

Détails

ID Serval
serval:BIB_F6E1698B4547
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Hemodynamic and humoral effects of the new renin inhibitor enalkiren in normal humans.
Périodique
Hypertension
Auteur(s)
Delabays A., Nussberger J., Porchet M., Waeber B., Hoyos P., Boger R., Glassman H., Kleinert H.D., Luther R., Brunner H.R.
ISSN
0194-911X
Statut éditorial
Publié
Date de publication
1989
Peer-reviewed
Oui
Volume
13
Numéro
6 Pt 2
Pages
941-7
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
The effect of the renin inhibitor enalkiren (Abbott-64662) was evaluated in eight normal volunteer subjects on a standardized sodium diet (100 mmol/day) by measurement of various components of the renin-angiotensin system and drug levels in plasma. On day 1, vehicle and doses of 0.001, 0.003, and 0.01 mg/kg i.v. were administered within 2 minutes at 90-minute intervals. On day 2, vehicle and doses of 0.01, 0.03, and 0.1 mg/kg i.v. were given. With the higher doses, blood pressure tended to decrease slightly with no change in heart rate. Plasma renin activity and plasma angiotensin-(1-8)octapeptide (angiotensin II) fell markedly in a dose-dependent manner. Inhibition of plasma renin activity was maximal 5 minutes after administration of the drug and persisted 90 minutes after the doses of 0.03 and 0.1 mg/kg. Not surprisingly, there was a close correlation between plasma renin activity and plasma angiotensin II levels (r = 0.81, n = 28, p less than 0.001). In contrast, active and total renin measured directly by monoclonal antibodies rose in dose-related fashion in response to renin inhibition. Pharmacokinetic parameters were calculated using the plasma drug concentrations obtained up to 6 hours after the 0.1 mg/kg dose. By means of a two-compartment model, plasma mean half-life of the drug was estimated at 1.60 +/- 0.43 hours.
Mots-clé
Adult, Angiotensin II, Dipeptides, Dose-Response Relationship, Drug, Hemodynamics, Humans, Injections, Intravenous, Reference Values, Renin
Pubmed
Web of science
Création de la notice
28/01/2008 10:48
Dernière modification de la notice
03/03/2018 22:49
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