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. 2024 Jan;13(1):111-116.
doi: 10.1002/cpdd.1336. Epub 2023 Nov 17.

Effect of the Phosphate Binder Sevelamer Carbonate on the Bioavailability of Enarodustat, an Oral Erythropoiesis Stimulating Agent

Sudhakar M Pai  1 , Hiroyuki Yamada  2
Affiliations

Effect of the Phosphate Binder Sevelamer Carbonate on the Bioavailability of Enarodustat, an Oral Erythropoiesis Stimulating Agent

Sudhakar M Pai et al. Clin Pharmacol Drug Dev. 2024 Jan.

Abstract

Enarodustat is an orally available hypoxia-inducible factor-prolyl hydroxylase inhibitor which can correct the erythropoietic capacity and improve anemia in chronic kidney disease. Sevelamer carbonate, a non-calcium-based polymeric resin, is one of the commonly prescribed agents for the management of hyperphosphatemia in patients undergoing hemodialysis. This was an open-label, crossover study in healthy male subjects (N = 12) that evaluated the effect of sevelamer carbonate (2400 mg) on the bioavailability of enarodustat (25 mg) when the 2 drugs were administered together (Treatment B) or when enarodustat was administered 3 hours after (Treatment C) or 1 hour before (Treatment D) sevelamer carbonate compared to enarodustat alone (Treatment A). With coadministration of the 2 drugs (Treatment B), enarodustat Cmax and AUCinf reductions were 53% and 45%, respectively. For Treatment C, Cmax and AUCinf reductions were 11% and 6%, respectively, and for Treatment D the corresponding values were 8% and 20%. Thus, coadministration of enarodustat and sevelamer carbonate resulted in a substantial reduction (≈50%) in the oral bioavailability of enarodustat. However, the interaction was substantially mitigated by staggering the administration of enarodustat and sevelamer carbonate. Administration of 4 single oral doses of enarodustat 25 mg, with or without sevelamer carbonate, were safe and well tolerated in this study.

Keywords: CKD; DDI; ESRD; HIF-PH; JTZ-951; clinical pharmacology; enarodustat; pharmacokinetics; sevelamer carbonate.

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