title: Pharmacokinetics of aluminoxamine and ferrioxamine and dose finding of desferrioxamine in haemodialysis patients.
abstract: We investigated the pharmacokinetics of desferrioxamine and its chelated compounds aluminoxamine and ferrioxamine in normal volunteers and haemodialysis patients with and without iron overload. Desferrioxamine was administered in a single dose of 30 mg per kg body-weight was a 30-min infusion to five healthy volunteers and to 20 haemodialysis patients (five patients without haemosiderosis and 15 patients with haemosiderosis). The interdialytic half-life of ferrioxamine was 2.2 h in normal volunteers, 13.3 h in dialysis patients without haemosiderosis, and 24.6 h in patients with haemosiderosis. There was no interdialytic elimination of aluminoxamine. In a second study, seven dialysis patients received 5, 10, and 20 mg per kg body-weight desferrioxamine in a random order with a time interval of 2 weeks. The peak serum concentrations after these doses were 4.1 +/- 2.9, 6.4 +/- 2.9, and 10.7 +/- 7.1 mumol/l for ferrioxamine and 2.8 +/- 1.5, 3.1 +/- 1.5, and 4.2 +/- 1.7 mumol/l for aluminoxamine. Thus, a 4-fold increase in desferrioxamine dosage resulted in a 2.7-fold increase in peak ferrioxamine levels and in only a 1.5-fold increase in peak aluminoxamine levels. We conclude that dialysis patients, especially those with haemosiderosis, are exposed to persistently elevated ferrioxamine levels. Weekly doses of 5-10 mg/kg of desferrioxamine would be sufficient for aluminium chelation therapy.
authors.affiliation: Department of Nephrology, University of Antwerp, Belgium.
authors.forename: G A
authors.initials: GA
authors.lastname: Verpooten
authors.forename: P C
authors.initials: PC
authors.lastname: D'Haese
authors.forename: J R
authors.initials: JR
authors.lastname: Boelaert
authors.forename: I
authors.initials: I
authors.lastname: Becaus
authors.forename: L V
authors.initials: LV
authors.lastname: Lamberts
authors.forename: M E
authors.initials: ME
authors.lastname: De Broe
mesh_terms: D000328:Adult; D000368:Aged; D000535:Aluminum / Q000378:metabolism; D002614:Chelating Agents / Q000493:pharmacokinetics*; D003676:Deferoxamine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005290:Ferric Compounds / Q000493:pharmacokinetics*; D006486:Hemosiderosis / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D009091:Mucormycosis / Q000139:chemically induced; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D006435:Renal Dialysis
chemical_list: D002614:Chelating Agents; D005290:Ferric Compounds; D009942:Organometallic Compounds; C002577:ferrioxamine B; C049544:aluminoxamine; D000535:Aluminum; D003676:Deferoxamine