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 more than 40 years,33 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 current use of DFO. This information has been supplemented since then by case reports and clinical experience. DFO is also used for chelation of aluminum in patients with chronic kidney failure. The merits of DFO as a treatment strategy for acute iron overdose is discussed in Chap. 46 and for aluminum toxicity in Chap. 87.
The development of DFO (or desferrioxamine B) resulted from an analysis of the iron containing metabolites of a species of actinomycetes. Ferrioxamine is a brownish-red compound containing trivalent iron (ferric, Fe3+) and three molecules of trihydroxamic acid isolated from the organism Streptomyces pilosus.38 DFO is the colorless compound that results when the trivalent iron is chemically removed from ferrioxamine B (Fig. A7–1).38
DFO is a water-soluble hexadentate chelator with a molecular weight of 561 Da. The commercial formulation is the mesylate salt with a molecular weight of 657 Da. One mole of DFO binds 1 mole of Fe3+; therefore, 100 mg DFO as the mesylate salt theoretically can bind 8.5 mg Fe3+.
DFO has a much greater affinity constant for iron (1031) and aluminum (1022) than for zinc, copper, nickel, magnesium, or calcium (102–1014).38 Thus, at physiologic pH, DFO complexes almost exclusively with ferric iron.28,84
Deferiprone, a bidentate oral iron chelator with a molecular weight of 139 Da, was approved by the US Food and Drug Administration (FDA) in 2011 for the treatment of iron overload in patients with thalassemia in whom current treatment is inadequate.24 Three moles of deferiprone are required to bind one mole of ferric ion to form a stable complex, which is excreted in the urine.32 Inappropriate ratios of drug to iron may be ineffective or even harmful because of the formation of potentially toxic intermediates.32 Preliminary animal studies of the use of deferiprone in acute iron toxicity are contradictory.10,23,36,39 A dose of 75 mg/kg deferiprone produces 60% of the total iron excretion that can be achieved with 50 mg/kg DFO. All of the iron eliminated with deferiprone occurs in the urine, while DFO eliminates iron in the urine and ...