PHARMACOKINETICS OF ALUMINOXAMINE AND FERRIOXAMINE AND DOSE FINDING OF DESFERRIOXAMINE IN HEMODIALYSIS-PATIENTS

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 as 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-mu-mol/l for ferrioxamine and 2.8 +/- 1.5, 3.1 +/- 1.5, and 4.2 +/- 1.7-mu-mol/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.