Fig 1.
Molecular formula of deferoxamine and speciation plots of its variously protonated forms.
Fig 2.
Molecular formula of deferiprone and speciation plots of its variously protonated forms.
Fig 3.
Molecular formula of exjade and speciation plots of its variously protonated forms.
Fig 4.
Speciation plots of the three ligands DFO, DFP and DFX and of their iron(III), copper(II) and zinc(II) complexes.
Ligand concentration: 10 μmol/L; metal concentration: 1 μmol/L.
Table 1.
Protonation and complex formation constants for DFO, DFP and DFX with iron(III), copper(II) and zinc(II) from literature.
Table 2.
Daily doses of iron chelators.
Table 3.
Speciation study of the systems “Albumin”-iron chelator-metal iron.
Concentration of the complexes formed between metal ions and iron chelators in presence of albumin, expressed as μmol/L. C1 and C2 represent the complexes MLH2 and MLH with DFO, and ML and ML2 with DFP and DFX.
Fig 5.
a) Plasma concentration of DFO (continuous line) reproduced on the basis of literature pharmacokinetic data [39] for a dose of 100 mg/Kg in 24 mL, administered at a rate of 1 mL per hour for 24 hours; the concentration of chelatable iron [25] is reported as red line. b) Plasma concentration of DFO (continuous line) for a dose of 100 mg/Kg in 12 mL, administered at a rate of 1 mL per hour for 12 hours. The concentration of chelatable iron [25], reported as red line, takes into account its increase when DFO is not administered.
Fig 6.
a) Plasma concentrations of DFP (continuous line) reproduced on the basis of literature pharmacokinetic data [41]; b) plasma concentrations of DFX (continuous line) reproduced on the basis of literature pharmacokinetic data [43]. In both cases a) and b) the concentration of chelatable iron [25] is reported as red line, and the stoichiometric ligand concentration needed to bind it as dashed line.
Table 4.
Speciation of different simulated conditions in the presence of the three different chelators.
Total concentrations of ligands, iron, zinc and copper (μmol/L) in species calculations are reported in columns 2 to 5, while the concentrations (μmol/L) of calculated complexed species (disregarding minor species) are reported in the remaining columns.