Bioavailability and stability of intravenous iron sucrose originator versus generic iron sucrose AZAD.

CONTEXT: Severe iron deficiency requires intravenous iron supplementation to replenish iron stores. Intravenous iron sucrose has been used for decades for the treatment of anemia. New generic iron sucrose products are now marketed for the use in several countries and there is an ongoing discussion about the safety and efficacy of iron sucrose similars. OBJECTIVE: In this study, we compared the iron sucrose originator Venofer® and the generic iron sucrose AZAD (ISA) regarding bioavailability, toxicity and stability in human THP-1 cells and HepG2 cells. METHODS: The bioavailability of Venofer® and ISA was investigated in both cell types by a ferrozin-based assay. The release of incorporated iron was assayed by atomic absorption spectroscopy. Ferritin content was measured by enzyme-linked immunosorbent assay (ELISA). HepG2 cells were used to investigate the intracellular labile iron pool (LIP), which was measured by the fluorescent calcein assay. The amount of redox-active iron within the iron formulations was assayed using fluorescent dichlorofluorescein. RESULTS: We found no significant differences in all parameters between Venofer® and ISA in regard of bioavailability, toxicity and stability in vitro. DISCUSSION: ISA shows identical physico-chemical features and identical bioavailability in vitro. This study is a profound basis for future clinical tests with generic iron sucrose compounds.

Intravenous iron preparations and ascorbic acid: effects on chelatable and bioavailable iron.

BACKGROUND: There is growing interest to use ascorbic acid as adjuvant therapy for patients with recombinant human erythropoietin-hyporesponsiveness (rHuEpo). Several clinical studies showed the beneficial effect of ascorbic acid treatment on hematologic parameters in rHuEpo-treated hemodialysis patients with elevated or even normal iron stores. However, whether ascorbic acid directly affects stability and cellular metabolism of intravenous iron preparations (IVI) is not well understood. METHODS: The preparations for testing were iron sucrose (Venofer), ferric gluconate (Ferrlecit), and iron dextran (INFeD). HepG2-cells were used to investigate effects of ascorbic acid on iron bioavailability for the intracellular labile iron pool (LIP) from IVI by using the fluorescent calcein-assay, and cellular ferritin content was measured by enzyme-linked immunosorbent assay (ELISA). Transferrin-chelatable iron was assessed by fluorescent-apotransferrin, and cell toxicity was assayed by neutral red cytotoxicity test. RESULTS: The effects of vitamin C on different preparations do not reflect their known chemical stability (i.e., iron dextran >iron sucrose >ferric gluconate). Effects of ascorbic acid on the increase of the intracellular LIP, as well as on increasing mobilization to transferrin in serum, were limited to iron sucrose. Ascorbic acid did not increase cell toxicity and the amount of low molecular weight iron in serum. CONCLUSION: We conclude that corrected ascorbic acid levels in hemodialysis (HD) patients could increase the amount of bioavailable iron from iron sucrose, but not from other classes of IVI. Vitamin C administration could therefore result in a lower need of iron sucrose to correct anemia.

Vitamin C: from popular food supplement to specific drug.

The daily requirement of a human person for vitamin C (ascorbic acid) has now been established at 100 mg. This value was already on the map when Arnold Durig put together the most important needs of nutritional ingredients. The modern value rests on the saturating level of ascorbate in leukocytes, which is in the millimolar range. The mechanism of accumulation of ascorbate in these cells rests on the uptake of oxidized dehydroascorbic acid. It is very efficient and avoids loss of vitamin which occurs in vitro when ascorbate is oxidized because of the great instability of the dehydro form. Therefore and increased requirement in case of infection is very unlikely from the biochemical point of view. However, low concentrations of ascorbate are found in patients suffering from arterial diseases or diseases accompanied by arterial damage such as diabetes mellitus. Ascorbate is known as a protection factor for the arterial endothel, but it is not clear by what mechanism this protection is brought about. Moreover, under clinical conditions very high concentrations are needed, which are achieved only by intravenous infusion, and the protection is only observed when the disease is manifest, not in healthy people. Therefore, also in this respect an increase in daily intake seems of no prophylactic value. Thus, by using high concentrations of ascorbate as an i.v. drug, effects of this substance frequently observed in vitro, could be used for therapy. This includes not only treatment of arterial diseases, but also relates to the cytotoxic effects of the vitamin against certain tumor cells and may assist conventional chemotherapy.