Safe Chelation of Iron

Assessment of the toxicity of a chelator should in principle be done in an adequate model of the target population of iron-loaded patients. Observations with subjects that lack excessive iron stores may be based on unrealistic concentrations of the uncomplexed chelator, or alternatively show effects of removal of needed baseline iron stores. For example, it is not yet clear whether toxic effects of the hydroxypyridones are an inherent property of the agents themselves, a result of chelation of iron or other trace elements at strategic cellular locations, or a consequence of the mobilization of iron in toxic form. Toxicity of these compounds in animal studies has not been observed to the same extent in significant experience with patients 

More significant is the risk of interorgan redistribution. Chelates forming in the hepatocyte may of course be transported into the bile and excreted in the feces. This is generally considered a positive attribute, but may simply reflect a limited ability to exit the cell. For instance, because ferrioxamine enters and exits cells with difficulty, almost all of the iron this agent removes from the body by biliary excretion (30%-50% of the total removed) originates in the hepatocyte (Hershko et al. 1978). Ferrioxamine that does make its way into the circulation from other sources is rapidly cleared by the kidney. On the one hand, this means that removal of iron 

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