Despite the clinical use of
deferoxamine for more than a quarter of a century, pharmacokinetic studies are few and have not been performed explicitly in patients with
sickle cell disorders. Early studies with
Intravenous administration to healthy volunteers and patients with transfusional overload showed that although peak concentrations of
deferoxamine were similar in both groups, concentrations of
ferrioxamine were higher in the latter. In
iron-overloaded patients with hereditary
hemochromatosis, an intramuscular 10 mg/kg bolus of
deferoxamine gave maximal plasma
ferrioxamine concentrations exceeding those of
deferoxamine, whereas in normal controls the reverse was the case. In more recent studies with homozygous
beta-thalassemia, using continuous Intravenous
deferoxamine infusion at 50 mg/kg/d, and initial elimination half-life of 0.28/h and steady-state concentration of 7 micromol/L were observed. In these studies, steady-state plasma levels of the predominant
deferoxamine metabolite B were usually lower than those of unmetabolized
deferoxamine. In a further
intravenous infusion study, the proportion of plasma metabolites was higher in those thalassaemia patients with low serum
ferritin levels relative to their current mean daily
deferoxamine dose, suggesting that high metabolite levels may predict excessive
desferrioxamine dosing. This hypothesis is supported by subcutaneous studies in which low doses of slow-release depot
deferoxamine resulted in significantly lower proportions of plasma metabolites than with conventional 8-hour infusions at 40 mg/kg. Because serum
ferritin is particularly unreliable as a marker of
iron overload in
sickle cell disorders, measurement of metabolites or the relative proportions of
deferoxamine and ferrloxamine may help identify patients at risk of excessive dosing. Because
iron overload is likely to become an increasing issue in patients with
sickle cell disorders, studies of the pharmacokinetics and metabolism of
deferoxamine in this patient group are needed.