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Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric 
 Oxyhydroxide

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Amount of radiolabelled iron found in red blood cells, liver, spleen and bone marrow in rats after a single dose administration of 59Fe-labelled sucroferric oxyhydroxide (50 mg Fe/kg bodyweight).
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Figure 3: Amount of radiolabelled iron found in red blood cells, liver, spleen and bone marrow in rats after a single dose administration of 59Fe-labelled sucroferric oxyhydroxide (50 mg Fe/kg bodyweight).

Mentions: Iron-replete rats and dogs were administered a 50 mg Fe/kg bodyweight dose of 59Fe radiolabelled sucroferric oxyhydroxide. For both groups of animals, a COBRA II Gamma Counter (Model 5003; Canberra Packard, Pangbourne, UK) with the capability to count low-level activity and higher energy isotopes was used to measure radioactivity. In rats, radioactivity was mainly found in the red blood cells (RBCs), with 0.62% of the total radioactivity from the administered dose found in these cells, corresponding to 78% of the total radioactivity retrieved. Some radioactivity was also found in the liver, amounting to 0.18% of the total from the administered dose and corresponding to 22% of the total amount of radioactivity retrieved (Fig. 3). Radioactivity was measured in dogs 7 days after administration. Similar to the findings in rats, 0.82% of the total radioactivity from the administered dose was found in RBCs, corresponding to 85% of the total amount of radioactivity retrieved. In one dog, 0.14% of the total radioactivity from the administered dose was found in the spleen, corresponding to 15% of the total amount of radioactivity retrieved in that animal. No radioactivity was found in two dogs. In both rats and dogs, 59Fe was excreted exclusively in the faeces.


Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric 
 Oxyhydroxide
Amount of radiolabelled iron found in red blood cells, liver, spleen and bone marrow in rats after a single dose administration of 59Fe-labelled sucroferric oxyhydroxide (50 mg Fe/kg bodyweight).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4997947&req=5

Figure 3: Amount of radiolabelled iron found in red blood cells, liver, spleen and bone marrow in rats after a single dose administration of 59Fe-labelled sucroferric oxyhydroxide (50 mg Fe/kg bodyweight).
Mentions: Iron-replete rats and dogs were administered a 50 mg Fe/kg bodyweight dose of 59Fe radiolabelled sucroferric oxyhydroxide. For both groups of animals, a COBRA II Gamma Counter (Model 5003; Canberra Packard, Pangbourne, UK) with the capability to count low-level activity and higher energy isotopes was used to measure radioactivity. In rats, radioactivity was mainly found in the red blood cells (RBCs), with 0.62% of the total radioactivity from the administered dose found in these cells, corresponding to 78% of the total radioactivity retrieved. Some radioactivity was also found in the liver, amounting to 0.18% of the total from the administered dose and corresponding to 22% of the total amount of radioactivity retrieved (Fig. 3). Radioactivity was measured in dogs 7 days after administration. Similar to the findings in rats, 0.82% of the total radioactivity from the administered dose was found in RBCs, corresponding to 85% of the total amount of radioactivity retrieved. In one dog, 0.14% of the total radioactivity from the administered dose was found in the spleen, corresponding to 15% of the total amount of radioactivity retrieved in that animal. No radioactivity was found in two dogs. In both rats and dogs, 59Fe was excreted exclusively in the faeces.

View Article: PubMed Central - PubMed

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.

No MeSH data available.