Deferasirox is an orally active, tridentate iron chelator with high selectivity for ferric iron (Fe3+). It binds iron in a 2:1 ligand-to-metal ratio, neutralises its redox activity and promotes elimination through the bile.
Tridentate Coordination Chemistry #
Each deferasirox molecule provides three coordination atoms (one phenolate oxygen and two nitrogen donors from the triazole ring system). Two molecules of deferasirox wrap around a single Fe3+ ion to form a stable, neutral hexacoordinate complex. Once formed, the deferasirox-iron complex is no longer redox-active - it cannot participate in Fenton-type reactions that generate hydroxyl radicals and drive tissue damage.
From Plasma to Bile #
Deferasirox is highly protein-bound (~99%), keeping it in the vascular compartment where it can intercept non-transferrin-bound iron and labile plasma iron pools. The deferasirox-iron complex is taken up by the liver and excreted into bile, with eventual loss in the faeces.
Selectivity for Fe3+ #
Deferasirox shows much higher binding affinity for Fe3+ than for biologically essential metals such as zinc and copper, contributing to its favourable mineral-balance profile in long-term therapy.
Tissue Iron Mobilisation #
By continuously lowering the labile iron pool, deferasirox creates a concentration gradient that mobilises iron from storage sites - particularly hepatocytes and, with sustained therapy, cardiomyocytes. Reductions in liver iron concentration (LIC) and serum ferritin are well-documented surrogate markers of clinical efficacy.
Clinical Translation #
The pharmacological design translates into a once-daily oral regimen suitable for long-term use in transfusion-dependent patients. The dispersible tablet format of DEFRATAJ supports accurate weight-based dosing and improved adherence compared with parenteral chelators.