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Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium Diet. | LitMetric

AI Article Synopsis

  • - Aprocitentan is being tested as a new oral medication to help manage difficult hypertension and its effects on weight gain were studied in healthy participants on a high-sodium diet.
  • - In a double-blind study with 28 subjects, those taking aprocitentan showed weight increases compared to placebo, with gains of up to 0.83 kg at the highest dose (50 mg/day).
  • - Despite the weight gain, there was no clear evidence of sodium retention; instead, plasma volume rose slightly, and urinary sodium excretion decreased at lower doses.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984323PMC
http://dx.doi.org/10.1002/cpt.2043DOI Listing

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