Limits...
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.


Related in: MedlinePlus

Iron release from sucroferric oxyhydroxide under conditions representative of administration on a full stomach during passage through the gastrointestinal tract [37]. *Average of duplicate samples. Observed changes in final pH values are due to buffering capacity of sucroferric oxyhydroxide and the dissolution process.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4997947&req=5

Figure 2: Iron release from sucroferric oxyhydroxide under conditions representative of administration on a full stomach during passage through the gastrointestinal tract [37]. *Average of duplicate samples. Observed changes in final pH values are due to buffering capacity of sucroferric oxyhydroxide and the dissolution process.

Mentions: In the second set of experiments, sucroferric oxyhydroxide showed minimal iron release (≤0.35%) across a pH range of 2.6–8.0 under conditions simulating being taken on a full stomach (Fig. 2) [37]. Although iron release was high (67%) at an initial pH of 1.2 (final pH 2.1) under conditions simulating administration on an empty stomach and in the absence of phosphate (conditions which are of a rather theoretical nature), this fell to just 6% under similar conditions (initial and final pH 1.2) in the presence of phosphate (Table 1).


Preclinical Pharmacokinetics, Pharmacodynamics and Safety of Sucroferric 
 Oxyhydroxide
Iron release from sucroferric oxyhydroxide under conditions representative of administration on a full stomach during passage through the gastrointestinal tract [37]. *Average of duplicate samples. Observed changes in final pH values are due to buffering capacity of sucroferric oxyhydroxide and the dissolution process.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Iron release from sucroferric oxyhydroxide under conditions representative of administration on a full stomach during passage through the gastrointestinal tract [37]. *Average of duplicate samples. Observed changes in final pH values are due to buffering capacity of sucroferric oxyhydroxide and the dissolution process.
Mentions: In the second set of experiments, sucroferric oxyhydroxide showed minimal iron release (≤0.35%) across a pH range of 2.6–8.0 under conditions simulating being taken on a full stomach (Fig. 2) [37]. Although iron release was high (67%) at an initial pH of 1.2 (final pH 2.1) under conditions simulating administration on an empty stomach and in the absence of phosphate (conditions which are of a rather theoretical nature), this fell to just 6% under similar conditions (initial and final pH 1.2) in the presence of phosphate (Table 1).

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.


Related in: MedlinePlus