om haemin containing substances including haemoglobin and transferrin. Since both ferrioxamine and aluminoxamine are completely excreted, Desferal promotes the excretion of iron and aluminium in urine and faeces, thus reducing pathological iron or aluminium deposits in the organs and tissues.
5.2 Pharmacokinetic properties
Absorption
Desferrioxamine is rapidly absorbed after intramuscular bolus injection or slow subcutaneous infusion, but is only poorly absorbed from the gastrointestinal tract in the presence of intact mucosa.
During peritoneal dialysis desferrioxamine is absorbed if administered in the dialysis fluid.
Distribution
In healthy volunteers peak plasma concentrations of desferrioxamine (15.5 micro mol/L (87 micro g/mL)) were measured 30 minutes after an intramuscular injection of 10 mg/kg desferrioxamine. One hour after injection the peak concentration of ferrioxamine was 3.7 micro mol/L (2.3 micro g/mL). Less than 10% of desferrioxamine is bound to serum proteins in vitro.
Biotransformation
Four metabolites of desferrioxamine were isolated from the urine of patients with iron overload. The following biotransformation reactions were found to occur with desferrioxamine: transamination and oxidation yielding an acid metabolite, beta-oxidation also yielding an acid metabolite, decarboxylation and N-hydroxylation yielding neutral metabolites.
Elimination
Both desferrioxamine and ferrioxamine a biphasic elimination after intramuscular injection in healthy volunteers; for desferrioxamine the apparent distribution half-life is 1 hour, and for ferrioxamine 2.4 hours. The apparent terminal half-life is 6 hours for both. Within six hours of injection, 22% of the dose appears in the urine as desferrioxamine and 1% as ferrioxamine.
Characteristics in patients
In patients with haemochromatosis peak plasma levels of 7.0 micro mol/L (3.9 micro g/mL) were measured for desferrioxamine, and 15.7 micro mol/L (9.6 micro g/mL) for ferrioxamine, 1 hour after an intramuscular injection of 10 mg/kg desferrioxamine. These patients eliminated desferrioxamine and ferrioxamine with half-lives of 5.6 and 4.6 hours respectively. Six hours after the injection 17% of the dose was excreted in the urine as desferrioxamine and 12% as ferrioxamine.
In patients dialysed for renal failure who received 40 mg/kg desferrioxamine infused i.v. within 1 hour, the plasma concentration at the end of the infusion was 152 micro mol/L (85.2 micro g/mL) when the infusion was given between dialysis sessions. Plasma concentrations of desferrioxamine were between 13% and 27% lower when the infusion was administered during dialysis. Concentrations of ferrioxamine were in all cases approximately 7.0 micro mol/L (4.3 micro g/mL) with concomitant aluminoxamine levels of 2-3 micro mol/litre (1.2-1.8 micro g/mL). After the infusion was discontinued, the plasma concentrations of desferrioxamine decreased rapidly with a half-life of 20 minutes. A smaller fraction of the dose was eliminated with a longer half-life of 14 hours. Plasma concentrations of aluminoxamine continued to increase for up to 48 hours post-infusion and reached values of approximately 7 micro mol/L (4 micro g/mL). Following dialysis the plasma concentration of aluminoxamine fell to 2.2 micro mol/L (1.3 micro g/mL), indicating that the aluminoxamine complex is dialysable.
In patients with thalassaemia continuous intravenous infusion of 50mg/kg/24h of desferr |
