A non-human primate model for the study of oral iron chelators.
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.
Wolfe
L C
LC
Department of Pediatrics, Floating Hospital for Infants and Children, New England Medical Center, Boston, Mass.
Nicolosi
R J
RJ
Renaud
M M
MM
Finger
J
J
Hegsted
M
M
Peter
H
H
Nathan
D G
DG
D000284:Administration, Oral; D000818:Animals; D002428:Cebus; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007273:Injections, Intramuscular; D007501:Iron / Q000097:blood* / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D004095:Dihydropyridines; D007502:Iron Chelating Agents; D013844:Thiazoles; D007501:Iron; D003676:Deferoxamine; C050223:desferrithiocin