Is There a Difference in the Preclinical Safety Parameters of Different Intravenous Iron Compounds?.

Intravenous (i.v.) iron has been effectively used to manage anemia in hemodialysis, chemotherapy-induced anemia and cardiac failure patients. However, i.v. iron preparations may cause different degree of oxidative stress and tissue inflammation. In the current study the effects of five i.v. iron preparations on haemodynamic, oxidative stress and inflammatory response were examined.

Sixty rats (n=10/group) received high molecular weight (HMW) iron dextran (Dexferrum®, American Regent, Inc., USA), low molecular weight (LMW) iron dextran (INFeD®, Watson Pharmaceuticals, USA/CosmoFer®, Vitaline Pharma, UK), ferric gluconate (Ferrlecit®, Watson Pharmaceuticals, USA), ferric carboxymaltose (Ferinject®, Vifor Pharma, Switzerland), iron sucrose (Venofer®, Vifor Pharma, Switzerland) or isotonic saline solution (control) in a blinded controlled study. Five i.v. doses of iron (40 mg iron/kg) or saline were administered over 4 weeks.

Systolic blood pressure was significantly reduced in the LMW dextran group, whereas serum iron and percentage transferrin saturation were significantly elevated in all treatment groups. Creatinine clearance was reduced and proteinuria increased in the ferric gluconate group only (p<0.01) (day 1 to 29). Liver enzyme levels in the blood were significantly increased in the ferric gluconate and two dextran groups on days 1, 8 and 29 compared with the ferric carboxymaltose and iron sucrose groups. Analysis of liver, heart and kidney homogenates on day 29 showed a significant increase in catalase and malondialdehyde levels in the ferric gluconate group, and an increase in CuZn-superoxide dismutase and glutathione peroxidase activity accompanied with a decrease in the reduced-to-oxidized glutathione ratio in the ferric gluconate and two dextran groups (p<0.01). TNF-α and IL6 levels were significantly elevated in liver, heart and kidney samples from the ferric gluconate and two dextran groups but not the ferric carboxymaltose, iron sucrose or control groups on day 29.

In this study, there was a difference in the hemodynamic and functional response to the different i.v. iron preparations. These findings indicate that HMW/LMW iron dextran and ferric gluconate have less favourable safety profiles in rats than ferric carboxymaltose and iron sucrose.

Toblli:Vifor Pharma: Research Funding.