Pharmacokinetics of desferrioxamine and of its iron and aluminium chelates in patients on haemodialysis

Abstract

We have used a new analytical micromethod to study the pharmacokinetics of desferrioxamine and its aluminium chelates in patients with chronic renal failure on haemodialysis. Desferrioxamine (Desferal, CIBA, Basle) was given by 1-h infusion just after the haemodialysis at 20, 40, 80 mg/kg body wt. and during the first and the last hour of the haemodialysis at 40 mg/kg. The concentrations of desferrioxamine during infusions showed a linear increase with increasing doses. The maximum concentrations and the AUC obtained when desferrioxamine was infused during the haemodialysis were not statistically different but slightly lower than those obtained in post dialysis administration. This result indicates that the loss of desferrioxamine by transfer in the dialysate is quite moderate within 1 h. During the interdialysis period, there was a decrease of plasma desferrioxamine concentrations with a mean half-life of 18.7 +/- 5.2 h and an increase in plasma concentrations of aluminium desferrioxamine chelate. In vitro studies show that a lengthy contact between desferrioxamine and plasma is necessary for complete chelation of A1 already present in plasma. During the following dialysis session, there was an important decrease of desferrioxamine and of its iron and aluminium chelates in blood plasma representing their transfer to the dialysis fluid.