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

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dc.identifier.uri http://dx.doi.org/10.15488/131
dc.identifier.uri http://www.repo.uni-hannover.de/handle/123456789/149
dc.contributor.author Gschwind, Hans-Peter
dc.contributor.author Schmid, Dietmar G.
dc.contributor.author Blanckenburg, Friedhelm von
dc.contributor.author Oelze, Marcus
dc.contributor.author Zuilen, Kirsten van
dc.contributor.author Slade, Alan J.
dc.contributor.author Stitah, Sylvie
dc.contributor.author Kaufmann, Daniel
dc.contributor.author Swart, Piet
dc.date.accessioned 2015-12-03T10:13:28Z
dc.date.available 2015-12-03T10:13:28Z
dc.date.issued 2014-07-14
dc.identifier.citation Gschwind, Hans-Peter; Schmid, Dietmar G.; von Blanckenburg, Friedhelm; Oelze, Marcus; van Zuilen, Kirsten; Slade, Alan J.; Stitah, Sylvie; Kaufmann, Daniel; Swart, Piet: Iron uptake and ferrokinetics in healthy male subjects of an iron-based oral phosphate binder (SBR759) labeled with the stable isotope Fe-58. In: Metallomics 6 (2014), Nr. 11, S. 2062-2071. DOI: http://dx.doi.org/10.1039/c4mt00126e
dc.description.abstract 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. eng
dc.language.iso eng eng
dc.publisher Cambridge : Royal Society of Chemistry
dc.relation.ispartofseries Metallomics 6 (2014), Nr. 11
dc.rights CC BY 3.0
dc.rights.uri http://creativecommons.org/licenses/by/3.0/
dc.subject chronic kidney-disease eng
dc.subject sevelamer hydrochloride eng
dc.subject lanthanum carbonate eng
dc.subject calcium-free eng
dc.subject erythrocyte incorporation eng
dc.subject dialysis patients eng
dc.subject nonheme iron eng
dc.subject normal women eng
dc.subject absorption eng
dc.subject efficacy eng
dc.subject.ddc 540 | Chemie ger
dc.title Iron uptake and ferrokinetics in healthy male subjects of an iron-based oral phosphate binder (SBR759) labeled with the stable isotope Fe-58 eng
dc.type article
dc.relation.essn 1756-591X
dc.relation.issn 1756-5901
dc.relation.doi http://dx.doi.org/10.1039/c4mt00126e
dc.bibliographicCitation.issue 11
dc.bibliographicCitation.volume 6
dc.bibliographicCitation.firstPage 2062
dc.bibliographicCitation.lastPage 2071
dc.description.version publishedVersion
tib.accessRights frei zug�nglich


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