A non‐human primate model for the study of oral iron chelators

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Abstract
Summary. 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 >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 μg (N=4), providing a low back ground 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.