Physicochemical properties of ferumoxytol, a new intravenous iron preparation.
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.


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 microM and 42 microg 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.
Balakrishnan
V S
VS
Tufts Medical Center, Boston, MA, USA. vbalakrishnan@tuftsmedicalcenter.org
Rao
M
M
Kausz
A T
AT
Brenner
L
L
Pereira
B J G
BJ
Frigo
T B
TB
Lewis
J M
JM
D000740:Anemia / Q000097:blood / Q000188:drug therapy*; D000818:Animals; D004334:Drug Administration Schedule; D052203:Ferrosoferric Oxide / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D007505:Iron-Dextran Complex / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy*; D008970:Molecular Weight; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats
D007505:Iron-Dextran Complex; D052203:Ferrosoferric Oxide