Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium Diet
| Autor: | Patricia N. Sidharta, Pierre Gueneau de Mussy, Marc Iglarz, Nicolas Guérard, Michel Burnier, Jasper Dingemanse, Grégoire Wuerzner, Marc Maillard, Bruno Flamion |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Endothelin Receptor Antagonists Male medicine.medical_specialty Administration Oral Natriuresis Placebo Weight Gain 030226 pharmacology & pharmacy Article Excretion 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Body Water Double-Blind Method Internal medicine Edema medicine Homeostasis Humans Pharmacology (medical) Aldosterone Aldosterone/blood Body Water/metabolism Cross-Over Studies Endothelin Receptor Antagonists/administration & dosage Endothelin Receptor Antagonists/adverse effects Glycopeptides/blood Healthy Volunteers Middle Aged Natriuresis/drug effects Pyrimidines/administration & dosage Pyrimidines/adverse effects Sodium Dietary/adverse effects Sulfonamides/administration & dosage Sulfonamides/adverse effects Switzerland Uric Acid/blood Water-Electrolyte Balance/drug effects Weight Gain/drug effects Pharmacology Sulfonamides Endothelin receptor antagonist business.industry Research Glycopeptides Sodium Dietary Articles Water-Electrolyte Balance Crossover study Uric Acid Endocrinology Pyrimidines chemistry 030220 oncology & carcinogenesis Uric acid Hemoglobin medicine.symptom business Weight gain |
| Zdroj: | Clinical pharmacology and therapeutics, vol. 109, no. 3, pp. 746-753 Clinical Pharmacology and Therapeutics |
| Popis: | Aprocitentan is a novel, oral, dual endothelin receptor antagonist (ERA) in development in difficult-to-control hypertension. As fluid retention and edema are concerns with ERAs, we investigated whether aprocitentan causes weight gain in healthy subjects on a high sodium diet and explored potential mechanisms if occurring. This double-blind, randomized, placebo-controlled, crossover study enrolled 28 subjects. Three doses of aprocitentan (10, 25, or 50 mg/day for 9 days) were compared with placebo. Increases in body weight were observed with aprocitentan (placebo-corrected mean weight gains [90% confidence interval]) of 0.43 [0.05-0.80], 0.77 [0.03-1.51], and 0.83 [0.33-1.32] kg at 10 mg, 25 mg, and 50 mg, respectively. Decreases in hemoglobin and uric acid were observed. Plasma volume increased at most by 5.5% without dose-response relationship. Urinary sodium excretion decreased at 10 mg and 25 mg but not at 50 mg. Therefore, aprocitentan produced moderate weight increases in healthy subjects on high sodium diet, without obvious sodium retention. |
| Databáze: | OpenAIRE |
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