Intravenous infusion pharmacokinetics of desferrioxamine in thalassaemic patients.
Pharmacokinetic investigation of desferrioxamine (DFO) was conducted in 11 thalassaemic patients following continuous intravenous infusion of 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 (59Fe) to stabilize free ligand forms of DFO and its metabolites. This resulted in the formation of both radioactive and nonradioactive forms of ferrioxamine and its metabolites. Following solid-phase extraction, plasma samples were analyzed by a reversed-phase HPLC and monitored by simultaneous UV-visible radioactive detection. DFO was found to be eliminated from the blood in a biexponential manner with a systemic clearance 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 the 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, DFO-metabolite B, has an initial half-life of 1.33 +/- 0.61 hr and is usually present at lower concentrations relative to the parent compound with an AUC of 191 +/- 106 mumol/liter.hr.
Lee
P
P
Department of Pharmacy, King's College London, University of London, United Kingdom.
Mohammed
N
N
Marshall
L
L
Abeysinghe
R D
RD
Hider
R C
RC
Porter
J B
JB
Singh
S
S
D002851:Chromatography, High Pressure Liquid; D003676:Deferoxamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D013056:Spectrophotometry, Ultraviolet; D013789:Thalassemia / Q000097:blood*
D003676:Deferoxamine