Labile iron in parenteral iron formulations: a quantitative and comparative study

Background. Evidence of iron-mediated oxidative stress. neutrophil dysfunction and enhanced bacterial growth after intravenous (IV) iron administration has been ascribed to a labile or bioactive iron fraction present in all IV iron agents. Methods. To quantify and compare the size of the labile fraction in several classes of IV iron agents, we examined iron donation to transferrin (Tf) in vitro. We added dilutions of ferric gluconate, iron sucrose and each of two iron dextran preparations to serum in vitro, passed the resulting samples through alumina columns to remove iron agent and free organic iron, and measured Tf-bound iron in the resulting eluates. Comparing results to serum samples without added iron, we calculated delta Tf-bound iron for each agent at each concentration. Finally, we compared delta Tf-bound iron to the concentration of added agent and calculated the percent iron donation to Tf. Results. We found that Tf-bound iron increased with added iron concentration for each agent: delta Tf-bound iron was directly related to the concentration and type of iron agent (P < 0.001). Mean percent iron donation to Tf ranged from 2.5 to 5.8% with the following progression: iron dextran-Dexferrum((R)) < iron dextran-INFeD(R) < iron sucrose < ferric gluconate. Pairwise differences between agents for percent iron donation were statistically significant (P<0.05) only between ferric gluconate and both iron dextran agents. and between iron sucrose and iron dextran-Dexferrum((R)). Conclusions. Approximately 2-6% of total iron in commonly used IV iron compounds is available for in vitro iron donation to Tf. This fraction may contribute to evidence of bioactive iron in patients after IV iron administration.