Iron uptake and ferrokinetics in healthy male subjects of an iron-based oral phosphate binder (SBR759) labeled with the stable isotope 58 Fe

Gschwind, Hans-Peter; Schmid, Dietmar G.; von Blanckenburg, Friedhelm; Oelze, Marcus; van Zuilen, Kirsten; Slade, Alan J.; Stitah, Sylvie; Kaufmann, Daniel; Swart, Piet (2014). Iron uptake and ferrokinetics in healthy male subjects of an iron-based oral phosphate binder (SBR759) labeled with the stable isotope 58 Fe. Metallomics, 6(11), pp. 2062-2071. Royal Society of Chemistry 10.1039/C4MT00126E

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SBR759 is a novel polynuclear iron(III) oxide–hydroxide starch·sucrose·carbonate complex being developed for oral use in chronic kidney disease (CKD) patients with hyperphosphatemia on hemodialysis. SBR759 binds inorganic phosphate released by food uptake and digestion in the gastro-intestinal tract increasing the fecal excretion of phosphate with concomitant reduction of serum phosphate concentrations. Considering the high content of ∼20% w/w covalently bound iron in SBR759 and expected chronic administration to patients, absorption of small amounts of iron released from the drug substance could result in potential iron overload and toxicity. In a mechanistic iron uptake study, 12 healthy male subjects (receiving comparable low phosphorus-containing meal typical for CKD patients: ≤1000 mg phosphate per day) were treated with 12 g (divided in 3 × 4 g) of stable 58Fe isotope-labeled SBR759. The ferrokinetics of [58Fe]SBR759-related total iron was followed in blood (over 3 weeks) and in plasma (over 26 hours) by analyzing with high precision the isotope ratios of the natural iron isotopes 58Fe, 57Fe, 56Fe and 54Fe by multi-collector inductively coupled mass spectrometry (MC-ICP-MS). Three weeks following dosing, the subjects cumulatively absorbed on average 7.8 ± 3.2 mg (3.8–13.9 mg) iron corresponding to 0.30 ± 0.12% (0.15–0.54%) SBR759-related iron which amounts to approx. 5-fold the basal daily iron absorption of 1–2 mg in humans. SBR759 was well-tolerated and there was no serious adverse event and no clinically significant changes in the iron indices hemoglobin, hematocrit, ferritin concentration and transferrin saturation.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Institute of Geological Sciences
08 Faculty of Science > Institute of Geological Sciences > Isotope Geology

UniBE Contributor:

van Zuilen, Kirsten

Subjects:

500 Science > 550 Earth sciences & geology
500 Science

ISSN:

1756-5901

Publisher:

Royal Society of Chemistry

Language:

English

Submitter:

Sarah Antenen

Date Deposited:

07 Aug 2015 14:03

Last Modified:

15 Apr 2019 16:23

Publisher DOI:

10.1039/C4MT00126E

BORIS DOI:

10.7892/boris.70741

URI:

https://boris.unibe.ch/id/eprint/70741

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