Recent studies have demonstrated that parenteral deferroxamine can prolong life in patients with
iron overload. We have developed a non-human primate model of
iron overload and have accurately determined negative
iron balance in parenteral and oral studies of deferroxamine and a new
chelator,
desferrithiocin. Cebus monkeys were loaded with
iron dextran (10 mg/kg twice weekly) until their serum contained a
transferrin saturation greater than 75%, and (in two animals) liver biopsies showed
iron loading. When complete
iron balance studies were performed at this time, basal
iron balance was -53 +/- 11 micrograms (N = 4), providing a low background for provocative studies.
Iron balance was determined for intramuscular (N = 2) and oral (N = 3) deferroxamine, as well as intramuscular (N = 1) and oral (N = 4)
desferrithiocin. The pattern of
iron excretion after parenteral deferroxamine strongly resembled that of the
iron-loaded, transfused human.
Desferrithiocin was found to have significant activity as an oral
chelator. This Cebus monkey model accurately determines negative
iron balance and readily permits precise comparison of
iron chelators given parenterally or orally. This model may offer an important step between rodent and human trials of promising new
iron chelators.