[SA-PO2433] Fe (III) Transfer from Soluble Ferric Pyrophosphate (SFP) to Human Apotransferrin

Ajay Gupta, Richard Yocum, Walter Holberg, Brian Mosley, Janelle Starr, Deanna Nelson, Alvin Crumbliss Rockwell Medical Technologies, Inc., Wixom, MI; Biolink Life Sciences, Inc., Cary, NC; Duke University, Durham, NC

Background: Parenteral iron administration is restricted to large polymeric iron-carbohydrate complexes stored and processed in the reticuloendothelial system (RE). Soluble ferric pyrophosphate (SFP) is the only simple iron salt appearing to be safe and effective for parenteral administration (Gupta et al., Kidney Int 1999;55:1891-8). If SFP delivers iron directly to human apotransferrin (apo-Tf), inflammation-induced RE block will be overcome and iron-induced redox reactions and iron acquisition by bacteria prevented. The kinetic efficiency of iron loading of apo-Tf at pH 7.4 provides a physico-chemical measure of iron bioavailability.
Methods: Kinetics of iron binding to apo-Tf from SFP compared to a ferric-nitrilotriacetic acid (NTA) were measured by UV absorbance at 470 nm, the absorbance maximum for holo-Tf by the method of Bates et al., J Biol Chem 1967;242(12):2810-5.
Results: Iron from SFP was taken up rapidly by apo-Tf, with more than 50% of iron uptake complete within one min and most of the iron bound within 10 min (Figure). SFP-derived iron is taken up by apo-Tf more rapidly than and with the same near quantitative efficiency as from ferric-NTA (a control material known to transfer iron rapidly and completely to transferrin).

Conclusion: These data suggest that SFP-derived iron is rapidly bioavailable and taken up by circulating apotransferrin within minutes of exposure. Clinical trials are underway to confirm that SFP can be effectively and safely administered via hemodialysis solution to ESRD patients.
Disclosure - grant/research support: Rockwell Medical Technologies, Inc; consultant: Rockwell Medical Technologies, Inc; scientific advisor: Rockwell Medical Technologies, Inc; ownership: Rockwell Medical Technologies, Inc; patent: Rockwell Medical Technologies, Inc

Saturday, October 31, 2009 10:00 AM

Poster Session: Dialysis: Anemia, Mechanisms, and Treatment II (10:00 AM-12:00 PM) Poster Board Number: SA-PO2433

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