An improved animal model for studying desferrioxamine.
A hamster model has been developed for studying desferrioxamine. The hamster shows many similarities to man in terms of plasma stability and metabolites formed from desferrioxamine. The [59Fe]ferritin derived from rats has been shown to be sequestered into liver parenchymal cells when injected intravenously into hamsters. The technique has proved sufficiently sensitive to enable detection of differences of < 1% of the radioactivity administered in the elimination of iron. Alterations in iron excretion were seen when dosing desferrioxamine via different routes. The principal route of iron excretion was into the intestines. The effectiveness of the dosing routes for desferrioxamine in removing iron were subcutaneous (10.5%) > intravenous (6.25%) > oral (3.66%) > control (2.19%). A dose-response relationship was demonstrated using the intravenous dose route. The model offers a simple method for comparing the efficacy of administration routes for determining the optimal use of desferrioxamine.
Steward
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A
Department of Drug Discovery, Ciba Pharmaceuticals, Horsham, West Sussex.
Williamson
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I
Madigan
T
T
Bretnall
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A
Hassan
I F
IF
D000818:Animals; D001345:Autoradiography; D006224:Cricetinae; D003676:Deferoxamine / Q000378:metabolism* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005293:Ferritins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008297:Male; D008954:Models, Biological; D051381:Rats
D005293:Ferritins; D003676:Deferoxamine