Iron sucrose and ferric carboxymaltose: no correlation between physicochemical stability and biological activity

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.