Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: Biodistribution after Intravenous Dosing in Rats.

Christopher Beekman,Murali Matta,Vikram Patel,Ashok Chockalingam,Sharron Stewart,Lin Xu,Rodney Rouse,Wenlei Jiang,Christopher Thomas,Adil Mohammad,Dajun Sun,Katherine Shea

doi:10.3390/nano8010010

Abstract

Relative biodistribution of FDA-approved innovator and generic sodium ferric gluconate (SFG) drug products was investigated to identify differences in tissue distribution of iron after intravenous dosing to rats. Three equal cohorts of 42 male Sprague-Dawley rats were created with each cohort receiving one of three treatments: (1) the innovator SFG product dosed intravenously at a concentration of 40 mg/kg; (2) the generic SFG product dosed intravenously at a concentration of 40 mg/kg; (3) saline dosed intravenously at equivalent volume to SFG products. Sampling time points were 15 min, 1 h, 8 h, 1 week, two weeks, four weeks, and six weeks post-treatment. Six rats from each group were sacrificed at each time point. Serum, femoral bone marrow, lungs, brain, heart, kidneys, liver, and spleen were harvested and evaluated for total iron concentration by ICP-MS. The ICP-MS analytical method was validated with linearity, range, accuracy, and precision. Results were determined for mean iron concentrations (µg/g) and mean total iron (whole tissue) content (µg/tissue) for each tissue of all groups at each time point. A percent of total distribution to each tissue was calculated for both products. At any given time point, the overall percent iron concentration distribution did not vary between the two SFG drugs by more than 7% in any tissue. Overall, this study demonstrated similar tissue biodistribution for the two SFG products in the examined tissues.

Highlights

Sodium ferric gluconate (SFG) is a colloidal iron parenteral product indicated for intravenous iron replacement therapy in patients with moderate to severe iron deficiency anemia, a commonNanomaterials 2018, 8, 10; doi:10.3390/nano8010010 www.mdpi.com/journal/nanomaterialsNanomaterials 2018, 8, 10 finding in chronic illness in advanced renal failure
Both the innovator (Ferrlecit®, Sanofi-Aventis U.S, Inc., Bridgewater, NJ, USA, lot A5075) and the generic (SFG Complex in Sucrose Injection, Watson Pharma Inc., Parsippany, NJ, USA, lot 142290.1) come in 62.5 mg, 5 mL single use vials at a concentration of 12.5 mg/mL
Since Inductively Coupled-Mass Spectrometry (ICP-MS) detection is indiscriminate to iron to iron species and source, endogenous iron would be present in every sample

Summary

Introduction

Sodium ferric gluconate (SFG) is a colloidal iron parenteral product indicated for intravenous iron replacement therapy in patients with moderate to severe iron deficiency anemia, a commonNanomaterials 2018, 8, 10; doi:10.3390/nano8010010 www.mdpi.com/journal/nanomaterialsNanomaterials 2018, 8, 10 finding in chronic illness in advanced renal failure. Sodium ferric gluconate (SFG) is a colloidal iron parenteral product indicated for intravenous iron replacement therapy in patients with moderate to severe iron deficiency anemia, a common. SFG nanoparticles are phagocytized by cells of the reticuloendothelial system (RES) where iron ions become part of the intracellular iron pool [5]. Non-transferrin bound iron (NTBI) can be found in the blood. NTBI is iron that is non- and loosely bound to blood proteins, sugars or others and that has the potential to participate in oxidation-reduction reactions, create reactive oxygen species and free radicals, and induce oxidative stress [6,8]. One of the safety concerns for SFG drug products is rate of iron release relative to transferrin saturation and the potential for oxidative stress

Methods

Discussion

Conclusion