title: Physico-chemical properties of the new generation IV iron preparations ferumoxytol, iron isomaltoside 1000 and ferric carboxymaltose.
abstract: The advantage of the new generation IV iron preparations ferric carboxymaltose (FCM), ferumoxytol (FMX), and iron isomaltoside 1000 (IIM) is that they can be administered in relatively high doses in a short period of time. We investigated the physico-chemical properties of these preparations and compared them with those of the older preparations iron sucrose (IS), sodium ferric gluconate (SFG), and low molecular weight iron dextran (LMWID). Mössbauer spectroscopy, X-ray diffraction, and Fe K-edge X-ray absorption near edge structure spectroscopy indicated akaganeite structures (β-FeOOH) for the cores of FCM, IIM and IS, and a maghemite (γ-Fe2O3) structure for that of FMX. Nuclear magnetic resonance studies confirmed the structure of the carbohydrate of FMX as a reduced, carboxymethylated, low molecular weight dextran, and that of IIM as a reduced Dextran 1000. Polarography yielded significantly different fingerprints of the investigated compounds. Reductive degradation kinetics of FMX was faster than that of FCM and IIM, which is in contrast to the high stability of FMX towards acid degradation. The labile iron content, i.e. the amount of iron that is only weakly bound in the polynuclear iron core, was assessed by a qualitative test that confirmed decreasing labile iron contents in the order SFG ≈ IS > LMWID ≥ FMX ≈ IIM ≈ FCM. The presented data are a step forward in the characterization of these non-biological complex drugs, which is a prerequisite to understand their cellular uptake mechanisms and the relationship between the structure and physiological safety as well as efficacy of these complexes.
authors: Chemical and Preclinical Research and Development, Vifor (International) Ltd., St. Gallen, Switzerland.
authors: Susann
authors: S
authors: Neiser
authors: Daniel
authors: D
authors: Rentsch
authors: Urs
authors: U
authors: Dippon
authors: Andreas
authors: A
authors: Kappler
authors: Peter G
authors: PG
authors: Weidler
authors: Jörg
authors: J
authors: Göttlicher
authors: Ralph
authors: R
authors: Steininger
authors: Maria
authors: M
authors: Wilhelm
authors: Michaela
authors: M
authors: Braitsch
authors: Felix
authors: F
authors: Funk
authors: Erik
authors: E
authors: Philipp
authors: Susanna
authors: S
authors: Burckhardt
mesh_terms: D002627:Chemistry, Physical; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry*; D005290:Ferric Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D052203:Ferrosoferric Oxide / Q000138:chemical synthesis / Q000737:chemistry*; D058085:Iron Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D008320:Maltose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D004187:Disaccharides; D005290:Ferric Compounds; D058085:Iron Compounds; C557707:iron isomaltoside 1000; C522335:ferric carboxymaltose; D008320:Maltose; D052203:Ferrosoferric Oxide