Physicochemical properties of ferumoxytol, a new intravenous iron preparation

• Published in: European journal of clinical investigation Vol. 39; no. 6; pp. 489 - 496
• Main Authors: Balakrishnan, V. S., Rao, M., Kausz, A. T., Brenner, L., Pereira, B. J. G., Frigo, T. B., Lewis, J. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2009; Wiley-Blackwell
• Subjects: Anemia - blood; Anemia - drug therapy; Animals; Biological and medical sciences; Bleomycin detectable iron; Drug Administration Schedule; Ferrosoferric Oxide - pharmacology; Ferrosoferric Oxide - therapeutic use; ferumoxytol; free iron; General aspects; Humans; Infusions, Intravenous; Iron-Dextran Complex - pharmacology; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - drug therapy; Medical sciences; Molecular Weight; osmolality; Oxidative Stress - drug effects; Rats; Antineoplastic agent; Intravenous administration; osmolality; Peptides; Free form; Iron; molecular weight; ferumoxytol; Inorganic element; Medicine; free iron; Antibiotic; Bleomycin; Glycopeptide; Preparation; Molecular mass; Bleomycin detectable iron; Physicochemical properties
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2009.02130.x

Background  Intravenous iron is a critical component of anaemia management. However, currently available preparations have been associated with the release of free iron, a promoter of bacterial growth and oxidative stress. Materials and methods  We determined the molecular weight, dialysability and capacity for free iron release of ferumoxytol, a semi‐synthetic carbohydrate‐coated superparamagnetic iron oxide nanoparticle. Ferumoxytol was compared with three intravenous iron preparations in clinical use: iron dextran (low molecular weight), sodium ferric gluconate and iron sucrose. Intravenous iron preparations were also incubated in rat, and pooled human sera (at concentrations of 600 μM and 42 μg mL−1 respectively) from healthy subjects. Results  The molecular weight of ferumoxytol was 731 kDa. The relative order of molecular weight was as follows: ferumoxytol > iron dextran > iron sucrose > sodium ferric gluconate. The least ultrafilterable iron was observed with ferumoxytol and the most with ferric gluconate. The least dialysable free iron was observed with ferumoxytol and the most with ferric gluconate. Incubation of intravenous iron preparations in rat or pooled human sera demonstrated minimal free iron release with ferumoxytol. The order of catalytic iron release as detected by the bleomycin detectable iron assay was as follows: ferumoxytol < iron dextran < iron sucrose < ferric gluconate. A similar trend was observed for the in vivo serum concentration of free iron in rats. Conclusions  In vitro observations from these experiments suggest that ferumoxytol has a favourable profile in terms of tendency to release free iron, in comparison with currently available intravenous iron preparations.