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.
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Authors | J Smolander, B Vogt, M Maillard, C Zweiacker, T Littke, T Hengelage, M Burnier |
Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 85
Issue 6
Pg. 628-34
(Jun 2009)
ISSN: 1532-6535 [Electronic] United States |
PMID | 19279566
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Electrolytes
- Endothelin Receptor Antagonists
- Pyridines
- Pyrimidines
- Sodium
- Avosentan
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Topics |
- Adolescent
- Adult
- Area Under Curve
- Blood Pressure
(drug effects)
- Body Weight
- Cross-Over Studies
- Dose-Response Relationship, Drug
- Electrolytes
(blood, urine)
- Endothelin Receptor Antagonists
- Glomerular Filtration Rate
(drug effects)
- Heart Rate
(drug effects)
- Humans
- Kidney
(blood supply, drug effects, physiology)
- Male
- Pyridines
(administration & dosage, adverse effects, pharmacokinetics)
- Pyrimidines
(administration & dosage, adverse effects, pharmacokinetics)
- Regional Blood Flow
(drug effects)
- Sodium
(metabolism)
- Young Adult
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