Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist.

Détails

ID Serval
serval:BIB_E42D7E65D381
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist.
Périodique
Clinical pharmacology and therapeutics
Auteur(s)
Munafo A., Christen Y., Nussberger J., Shum L.Y., Borland R.M., Lee R.J., Waeber B., Biollaz J., Brunner H.R.
ISSN
0009-9236
Statut éditorial
Publié
Date de publication
1992
Peer-reviewed
Oui
Volume
51
Numéro
5
Pages
513-21
Langue
anglais
Notes
Publication types: Clinical Trial ; Controlled Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
The aim of this study was to investigate the relationships between plasma concentrations of losartan, an orally active angiotensin II inhibitor, its active metabolite EXP3174, and angiotensin II blockade. Six healthy subjects received single oral doses of 40, 80, or 120 mg losartan and placebo at 1-week intervals in a crossover study. Angiotensin II blockade was assessed by the blood pressure response to exogenous angiotensin II before and after losartan administration. EXP3174 reached higher plasma concentrations and was eliminated more slowly than its parent compound; its levels paralleled the profile of angiotensin II blockade closer than losartan. Inhibition of the pressure response was dose dependent. The Hill-shaped relationship between response and EXP3174 concentration (or time-integrated variables) approached a plateau with 80 mg. The dose-dependent increase in plasma renin and angiotensin II exhibited a considerable individual scatter. We conclude that losartan produces a dose-dependent, effective angiotensin II blockade that is largely determined by the active metabolite EXP3174.
Mots-clé
Administration, Oral, Adult, Aldosterone, Analysis of Variance, Angiotensin II, Antihypertensive Agents, Biotransformation, Biphenyl Compounds, Blood Pressure, Dose-Response Relationship, Drug, Humans, Imidazoles, Losartan, Male, Receptors, Angiotensin, Reference Values, Renin, Tetrazoles
Pubmed
Web of science
Création de la notice
25/01/2008 10:41
Dernière modification de la notice
20/08/2019 16:07
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