title: Iron sucrose and ferric carboxymaltose: no correlation between physicochemical stability and biological activity.
abstract: Intravenous iron preparations, like iron sucrose (IS) and ferric carboxymaltose (FCM) differ in their physicochemical stability. Thus differences in storage and utilization can be expected and were investigated in a non-clinical study in liver parenchyma HepG2-cells and THP-1 macrophages as models for toxicological and pharmacological target cells. HepG2-cells incorporated significant amounts of IS, elevated the labile iron pool (LIP) and ferritin and stimulated iron release. HepG2-cells had lower basal cellular iron and ferritin content than THP-1 macrophages, which showed only marginal accumulation of IS and FCM. However, FCM increased the LIP up to twofold and significantly elevated ferritin within 24 h in HepG2-cells. IS and FCM were non-toxic for HepG2-cells and THP-1 macrophages were more sensitive to FCM compared to IS at all concentrations tested. In a cell-free environment redox-active iron was higher with IS than FCM. Biostability testing via assessment of direct transfer to serum transferrin did not reflect the chemical stability of the complexes (i.e., FCM > IS). Effect of vitamin C on mobilisation to transferrin was an increase with IS and interestingly a decrease with FCM. In conclusion, FCM has low bioavailability for liver parenchyma cells, therefore liver iron deposition is unlikely. Ascorbic acid reduces transferrin-chelatable iron from ferric carboxymaltose, thus effects on hepcidin expression should be investigated in clinical studies.
authors.affiliation: Department of Medical Chemistry, Medical University of Vienna, Waehringerstr. 10, 1090, Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Praschberger
authors.forename: Kathrin
authors.initials: K
authors.lastname: Haider
authors.forename: Carolin
authors.initials: C
authors.lastname: Cornelius
authors.forename: Markus
authors.initials: M
authors.lastname: Schitegg
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sturm
authors.forename: Hans
authors.initials: H
authors.lastname: Goldenberg
authors.forename: Barbara
authors.initials: B
authors.lastname: Scheiber-Mojdehkar
mesh_terms: D001205:Ascorbic Acid / Q000378:metabolism; D002460:Cell Line; D005290:Ferric Compounds / Q000494:pharmacology*; D000077605:Ferric Oxide, Saccharated; D005293:Ferritins / Q000378:metabolism; D005937:Glucaric Acid / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008320:Maltose / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D005290:Ferric Compounds; C522335:ferric carboxymaltose; D008320:Maltose; D005293:Ferritins; D007501:Iron; D000077605:Ferric Oxide, Saccharated; D001205:Ascorbic Acid; D005937:Glucaric Acid