Kinetics and efficacy of deferoxamine in iron-overloaded hemodialysis patients.
We evaluated the kinetics and efficacy of deferoxamine (DFO) therapy in iron-overloaded hemodialysis patients. Concentrations of DFO and its chelated product, feroxamine (Fx), were assessed following single-dose DFO administration in twelve patients, and during chronic therapy over one year's time in eight, similarly iron-overloaded dialysis patients. A functional assay which relies on measurements of iron and iron binding capacity for the determination of Fx and DFO, respectively, was corroborated with liquid chromatographic techniques. Half-life measurements were also corroborated with tracer doses of 14C-DFO and 59Fe-feroxamine. Intradialytic DFO half-life (2.3 +/- 1.1 h) was considerably less than interdialytic half-life (26 +/- 1 hr). Unbound DFO was found to persist throughout the interdialytic period. Calculation of the percent saturation of the DFO dose indicated that only 30% of a given dose is chelated. The amount of iron removed dialytically was approximately 13.1 +/- 2.7 mg per dialysis session. Chronic DFO administration was also shown to enhance gastrointestinal iron excretion threefold. However, ferritin levels decreased by only 25% after one year of thrice-weekly DFO therapy. We conclude that DFO therapy for iron-overloaded hemodialysis patients is optimized by its administration interdialytically, and results in slow removal of iron, via both dialytic and gastrointestinal routes.
Stivelman
J
J
Department of Medicine, University of Arizona Health Sciences Center, Tucson.
Schulman
G
G
Fosburg
M
M
Lazarus
J M
JM
Hakim
R M
RM
D000328:Adult; D003676:Deferoxamine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D005290:Ferric Compounds / Q000493:pharmacokinetics; D006801:Humans; D007501:Iron / Q000009:adverse effects* / Q000378:metabolism; D007502:Iron Chelating Agents / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013997:Time Factors
D005290:Ferric Compounds; D007502:Iron Chelating Agents; C002577:ferrioxamine B; D007501:Iron; D003676:Deferoxamine