Abstract
A number of reports have appeared in literature calling attention to the depletion of essential metal ions during chelation therapy on β-thalassaemia patients. We present a speciation study to determine how the iron chelators used in therapy interfere with the homeostatic equilibria of essential metal ions. This work includes a thorough analysis of the pharmacokinetic properties of the chelating agents currently in clinical use, of the amounts of iron, copper and zinc available in plasma for chelation, and of all the implied complex formation constants. The results of the study show that a significant amount of essential metal ions is complexed whenever the chelating agent concentration exceeds the amount necessary to coordinate all disposable iron —a frequently occurring situation during chelation therapy. On the contrary, copper and zinc do not interfere with iron chelation, except for a possible influence of copper on iron speciation during deferiprone treatment.
Highlights
Iron chelation therapy is a life-long treatment for blood-transfused β-thalassaemia patients
Any disturbance of the homeostatic equilibria of essential metal ions in the body induced by chelating agents can lead to serious health consequences
In this work we carefully examine, from a thermodynamic perspective, the complexation of iron(III), zinc(II), and copper(II) by the three ligands employed in clinical treatment of iron overload, under simulated conditions
Summary
Iron chelation therapy is a life-long treatment for blood-transfused β-thalassaemia patients. To calculate the speciation of our three metal ions of interest in human plasma—the target of chelation, iron(III), and the essential metal ions copper(II) and zinc(II)–in presence of each of the chelating agents DFO, DFP, and DFX, the protonation and complex formation constants of all these ligands with the metal ions of interest have to be known.
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