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Deferoxamine (DFO) is the parenteral chelator of choice for treatment of acute iron poisoning. Considering that DFO has been used to treat patients with acute iron overdose for a little over 40 years,30 there is still much that is unknown. No controlled studies have evaluated the efficacy or dosing of DFO. Animal studies and case series from the 1960s and 1970s form the basis for how we use DFO. This information has been supplemented since then by limited case reports and clinical experience. DFO is also used for chelation of aluminum in patients with chronic renal failure. The merits of DFO as a treatment strategy for acute iron overdose is discussed in Chapter 40 and for aluminum toxicity in Chapter 86.

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The development of DFO (or desferrioxamine B) resulted from an analysis of the iron containing metabolites of a species of actinomycetes. DFO is the colorless compound that results when the trivalent iron is chemically removed from ferrioxamine B (Fig. A7–1).35 Ferrioxamine is a brownish-red compound containing trivalent iron (ferric, Fe3+) and three molecules of trihydroxamic acid isolated from the organism Streptomyces pilosus.35

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DFO is a water-soluble hexadentate chelator with a molecular weight of 561 daltons. The commercial formulation is the mesylate salt with a molecular weight of 657 daltons. One mole of DFO binds 1 mole of Fe3+; therefore, 100 mg DFO as the mesylate salt theoretically can bind 8.5 mg Fe3+.

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DFO has a much greater affinity constant for iron (1031) and aluminum (1022) than for zinc, copper, nickel, magnesium, or calcium (102–1014).35 Thus, at physiologic pH, DFO complexes almost exclusively with ferric iron.26,75

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DFO binds Fe3+ at the 3 N–OH sites, forming an octahedral iron complex (see Fig. A7–1). Once bound, the resultant ferrioxamine is very stable. DFO appears to benefit iron-poisoned patients by chelating free iron (nontransferrin plasma iron) and iron in transit between transferrin and ferritin (labile chelatable iron pool)29,41,58 while not directly affecting the iron of hemoglobin, hemosiderin, or ferritin.35 Although in vitro studies suggest that DFO removes iron from ferritin and transferrin with only very little from hemosiderin,46 in vivo experiments demonstrate that DFO cannot remove iron after the iron is bound to transferrin.4 DFO does bind "free iron" found in the plasma as nontransferrin plasma iron after transferrin saturation, which only occurs acutely after overdose or chronically in iron overload syndromes.29 In vitro studies demonstrate that DFO chelates and inactivates cytoplasmic, lysosomal, and probably mitochondrial iron, preventing disruption of mitochondrial function and injury.25,41 An in vitro study suggests that DFO gains access to cytosol and endosomes through endocytosis rather ...

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