Dose-dependent acute and sustained renal effects of the endothelin receptor antagonist avosentan in healthy subjects.

Details

Serval ID
serval:BIB_11E8FF45CFE0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dose-dependent acute and sustained renal effects of the endothelin receptor antagonist avosentan in healthy subjects.
Journal
Clinical Pharmacology and Therapeutics
Author(s)
Smolander J., Vogt B., Maillard M., Zweiacker C., Littke T., Hengelage T., Burnier M.
ISSN
1532-6535[electronic]
Publication state
Published
Issued date
2009
Volume
85
Number
6
Pages
628-634
Language
english
Abstract
The endothelin receptor antagonist avosentan may cause fluid overload at doses of 25 and 50 mg, but the actual mechanisms of this effect are unclear. We conducted a placebo-controlled study in 23 healthy subjects to assess the renal effects of avosentan and the dose dependency of these effects. Oral avosentan was administered once daily for 8 days at doses of 0.5, 1.5, 5, and 50 mg. The drug induced a dose-dependent median increase in body weight, most pronounced at 50 mg (0.8 kg on day 8). Avosentan did not affect renal hemodynamics or plasma electrolytes. A dose-dependent median reduction in the fractional renal excretion of sodium was found (up to 8.7% at avosentan 50 mg); this reduction was paralleled by a dose-related increase in proximal sodium reabsorption. It is suggested that avosentan dose-dependently induces sodium retention by the kidney, mainly through proximal tubular effects. The potential clinical benefits of avosentan should therefore be investigated at doses of <or= 5 mg.
Keywords
Adolescent, Adult, Area Under Curve, Blood Pressure/drug effects, Body Weight, Cross-Over Studies, Dose-Response Relationship, Drug, Electrolytes/blood, Electrolytes/urine, Glomerular Filtration Rate/drug effects, Heart Rate/drug effects, Humans, Kidney/blood supply, Kidney/drug effects, Male, Pyridines/administration & dosage, Pyridines/adverse effects, Pyrimidines/administration & dosage, Pyrimidines/adverse effects, Receptors, Endothelin/antagonists & inhibitors, Regional Blood Flow/drug effects, Sodium/metabolism, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
27/06/2009 14:09
Last modification date
20/08/2019 12:39
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