Pharmacokinetic and pharmacodynamic effects of YM087, a combined V1/V2 vasopressin receptor antagonist in normal subjects.

Détails

ID Serval
serval:BIB_3C8E35FC3287
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Pharmacokinetic and pharmacodynamic effects of YM087, a combined V1/V2 vasopressin receptor antagonist in normal subjects.
Périodique
European journal of clinical pharmacology
Auteur⸱e⸱s
Burnier M., Fricker A.F., Hayoz D., Nussberger J., Brunner H.R.
ISSN
0031-6970
Statut éditorial
Publié
Date de publication
1999
Peer-reviewed
Oui
Volume
55
Numéro
9
Pages
633-7
Langue
anglais
Notes
Publication types: Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
OBJECTIVE: The pharmacokinetic and pharmacodynamic properties of YM087, (4'-[(2-methyl-1,4,5,6- tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)-carbonyl]-2-p henylbenzanilide monohydrochloride), a new orally active, dual V1/V2 receptor antagonist were characterised in healthy normotensive subjects. METHODS: Six subjects were randomly allocated to receive, at 1-week intervals, a single oral dose of 60 mg YM087 and a single i.v. dose of 50 mg YM087 in an open-label, crossover study. RESULTS: YM087 had an oral bioavailability of 44% and a short half-life. Upon oral and i.v. administration of YM087, a significant sevenfold increase in urine flow rate and a fall in urinary osmolality (from 600 mosmol/l to less than 100-mosmol/l) were observed with a peak effect 2 h after drug intake suggesting effective vasopressin V2 receptor blockade. Simultaneously, significant increases in plasma osmolality (from 283 +/- 1.3 mosmol/l to 288 +/- 1.0 mosmol/l after i.v. and from 283 +/- 2.1 mosmol/l to 289 +/- 1.7-mosmol/l after oral administration) and vasopressin levels (from 1.5 +/- 0.3 pg/ml to 3.7 +/- 0.6 pg/ml after i.v. and from 0.9 +/- 0.1 pg/ml to 3.9 +/- 0.7 pg/ml after oral administration) were found. When administered i.v., YM087 inhibited the vasopressin-induced skin vasoconstriction, suggesting a blockade of V1 receptors. However, the YM087-induced antagonism of V1 receptors was less pronounced than V2 receptor blockade. CONCLUSION: These data show that YM087 is an effective dual V1/V2 receptor antagonist in man.
Mots-clé
Administration, Oral, Adult, Benzazepines, Biological Availability, Cross-Over Studies, Half-Life, Humans, Injections, Intravenous, Male, Osmolar Concentration, Receptors, Vasopressin, Reference Values, Skin, Vasoconstriction, Water-Electrolyte Balance
Pubmed
Web of science
Création de la notice
17/01/2008 17:38
Dernière modification de la notice
20/08/2019 14:32
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