Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium Diet. Issue 3 (29th September 2020)

• Record Type: Journal Article
• Authors: Gueneau de Mussy, Pierre; Sidharta, Patricia N.; Wuerzner, Gregoire; Maillard, Marc P.; Guérard, Nicolas; Iglarz, Marc; Flamion, Bruno; Dingemanse, Jasper; Burnier, Michel
• Is Part Of: Clinical pharmacology & therapeutics. Volume 109:Issue 3(2021)
• Page Start: 746
• Page End: 753
• Publication Date: 2020-09-29
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1002/cpt.2043
• Languages: English
• ISSNs: 0009-9236

Abstract

Abstract : 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.