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: G A Verpooten, P C D'Haese, J R Boelaert, I Becaus, L V Lamberts, M E De Broe
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 7 Issue 9 Pg. 931-8 ( 1992) ISSN: 0931-0509 [Print] England
• PMID: 1328941 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Chelating Agents
• Ferric Compounds
• Organometallic Compounds
• ferrioxamine B
• aluminoxamine
• Aluminum
• Deferoxamine

Topics

• Adult
• Aged
• Aluminum (metabolism)
• Chelating Agents (pharmacokinetics)
• Deferoxamine (administration & dosage, adverse effects, pharmacokinetics)
• Ferric Compounds (pharmacokinetics)
• Hemosiderosis (metabolism)
• Humans
• Liver (metabolism)
• Middle Aged
• Mucormycosis (chemically induced)
• Organometallic Compounds (pharmacokinetics)
• Renal Dialysis