Research Area: Cardiovascular Disease Biological Activity: Deferasirox(Exjade) is a rationally-designed oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long-term blood transfusions for conditions such as beta-thalassemia and other chronic anemias. The half-life of deferasirox is between 8 and 16 hours allowing once a day dosing. [1]
Deferasirox is an oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long term blood transfusions for conditions such as beta-thalassemia and other chronic anemias. It is the first oral medication approved in the USA for this purpose.
Indication
For the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in patients 2 years of age and older.
Pharmacology
Deferasirox is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Although deferasirox has very low affinity for zinc and copper there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. The clinical significance of these decreases is uncertain.
Affected Organisms
Humans and other mammals
Biotransformation
Hepatic. CYP450-catalyzed (oxidative) metabolism of deferasirox appears to be minor in humans (about 8%). Glucuronidation is the main metabolic pathway for deferasirox, with subsequent biliary excretion.
Absorption
The absolute bioavailability (AUC) of deferasirox tablets for oral suspension is 70% compared to an intravenous dose.
Half Life
The mean elimination half-life ranged from 8 to 16 hours following oral administration.
Protein Binding
Deferasirox is highly (~99%) protein bound almost exclusively to serum albumin.
Elimination
Deferasirox and metabolites are primarily (84% of the dose) excreted in the feces. Renal excretion of deferasirox and metabolites is minimal (8% of the administered dose).
A member of the class of triazoles, deferasirox is 1,2,4-triazole substituted by a 4-carboxyphenyl group at position 1 and by 2-hydroxyphenyl groups at positions 3 and 5. An orally active iron chelator, it is used to manage chronic iron overload in patients receiving long-term blood transfusions.
