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Curr Drug Metab. 2014;15(10):953-65.

Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric Oxyhydroxide.

Author information

1
Department of Health Sciences, University of Milan, Renal Division, San Paolo Hospital, Via A. Di Rudinì, 8 20142 Milan, Italy. mario.cozzolino@unimi.it.

Abstract

Sucroferric oxyhydroxide (VELPHORO) is a polynuclear iron-based phosphate binder recently approved for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). As a number of the available phosphate binders do not provide the optimal combination of good efficacy, adequate tolerability and low pill burden, sucroferric oxyhydroxide constitutes a promising alternative. Among the attributes of an ideal phosphate binder is minimal absorption and, hence, low risk of systemic toxicity. Accordingly, the iron-releasing properties and absorption, distribution, metabolism and excretion (ADME) profile of sucroferric oxyhydroxide, as well as the possibility of iron accumulation and toxicity, were investigated in a series of preclinical studies. The effect of sucroferric oxyhydroxide on the progression of vascular calcification was also investigated. Sucroferric oxyhydroxide exhibited a high phosphate-binding capacity and low iron-releasing properties across the physiological pH range found in the gastrointestinal tract. In the ADME studies, uptake of (59)Fe-radiolabelled sucroferric oxyhydroxide was low in rats and dogs (<1% from a 50 mg Fe/kg bodyweight dose), with the majority of absorbed iron located in red blood cells. Long-term (up to 2 years) administration of sucroferric oxyhydroxide in rats and dogs was associated with modest increases in tissue iron levels and no iron toxicity. Moreoever, in uraemic rats, sucroferric oxyhydroxide was associated with reduced progression of vascular calcification compared with calcium carbonate. In conclusion, sucroferric oxyhydroxide offers a new option for the treatment of hyperphosphataemia, with a high phosphate-binding capacity, minimal iron release, and low potential for iron accumulation and toxicity.

PMID:
25658128
PMCID:
PMC4997947
DOI:
10.2174/1389200216666150206124424
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Mario Cozzolino has received research grants from Abbvie and Shire. He has attended advisory boards for Abbvie, Amgen, Genzyme/Sanofi, Keryx, Shire and Vifor Pharma/Fresenius Medical Care, and has received lecture honoraria from Abbvie, Amgen, Genzyme/Sanofi, Roche and Shire. Isaac Teitelbaum attended an advisory board for Vifor Pharma. Olivier Phan received congress travel expenses cover from Vifor (International) Ltd., St. Gallen. Viatcheslav Rakov and Felix Funk are employees of Vifor Pharma Ltd. This review article was funded by Vifor Pharma Ltd.

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