INTRAVENOUS-INFUSION PHARMACOKINETICS OF DESFERRIOXAMINE IN THALASSEMIC PATIENTS

Pharmacokinetic investigation of desferrioxamine (DFO) was conducted i n 11 thalassaemic patients following continuous intravenous infusion o f 50 mg/kg/24 hr over 48 hr. Serial venous blood samples were obtained at regular time intervals during and on stopping DFO infusion. Plasma samples were processed with the addition of radioactive iron (Fe-59) to stabilize free ligand forms of DFO and its metabolites. This result ed in the formation of both radioactive and nonradioactive forms of fe rrioxamine and its metabolites. Following solid-phase extraction, plas ma samples were analyzed by a reversed-phase HPLC and monitored by sim ultaneous UV-visible radioactive detection. DFO was found to be elimin ated from the blood in a biexponential manner with a systemic clearanc e of 0.50 +/- 0.24 liters/hr/kg. The terminal half-life was 3.05 +/- 1 .30 hr, and the volume of distribution was 1.88 +/- 1.0 liters/kg at t he terminal phase and 1.35 +/- 0.65 liters/kg at steady state. The AUC of DFO was 354 +/- 131 mumol/liter.hr. The major metabolite of DFO, D FO-metabolite B, has an initial half-life of 1.33 +/- 0.61 hr and is u sually present at lower concentrations relative to the parent compound with an AUC of 191 +/- 106 mumol/liter.hr.