A Speciation Study on the Perturbing Effects of Iron Chelators on the Homeostasis of Essential Metal Ions

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.