Porter J B
Department of Haematology, University College of London, England.
Semin Hematol. 2001 Jan;38(1 Suppl 1):63-8. doi: 10.1016/s0037-1963(01)90061-7.
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.
