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Effect of the Phosphate Binder Sevelamer Carbonate on the Bioavailability of Enarodustat, an Oral Erythropoiesis Stimulating Agent.
- Source :
-
Clinical pharmacology in drug development [Clin Pharmacol Drug Dev] 2024 Jan; Vol. 13 (1), pp. 111-116. Date of Electronic Publication: 2023 Nov 17. - Publication Year :
- 2024
-
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 C <subscript>max</subscript> and AUC <subscript>inf</subscript> reductions were 53% and 45%, respectively. For Treatment C, C <subscript>max</subscript> and AUC <subscript>inf</subscript> 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.<br /> (© 2023, The American College of Clinical Pharmacology.)
- Subjects :
- Humans
Male
Sevelamer
Biological Availability
Cross-Over Studies
Phosphates
Hematinics
Subjects
Details
- Language :
- English
- ISSN :
- 2160-7648
- Volume :
- 13
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical pharmacology in drug development
- Publication Type :
- Academic Journal
- Accession number :
- 37975611
- Full Text :
- https://doi.org/10.1002/cpdd.1336