Title:Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric Oxyhydroxide
VOLUME: 15 ISSUE: 10
Author(s):Mario Cozzolino, Felix Funk, Viatcheslav Rakov, Olivier Phan and Isaac Teitelbaum
Affiliation:Department of Health Sciences, University of Milan, Renal Division, San Paolo Hospital, Via A. Di Rudinì, 8 20142 Milan, Italy.
Keywords:Chronic kidney disease (CKD), dialysis, hyperphosphataemia, phosphate, phosphate binder, preclinical, sucroferric oxyhydroxide.
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 59Fe-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.
