Safety and efficacy of combined chelation therapy with deferasirox and deferoxamine in a gerbil model of iron overload.
BACKGROUND
Combined therapy with deferoxamine (DFO) and deferasirox (DFX) may be performed empirically when DFX monotherapy fails. Given the lack of published data on this therapy, the study goal was to assess the safety and efficacy of combined DFO/DFX therapy in a gerbil model.


METHODS
Thirty-two female Mongolian gerbils 8-10 weeks old were divided into 4 groups (sham chelated, DFO, DFX, DFO/DFX). Each received 10 weekly injections of 200 mg/kg iron dextran prior to initiation of 12 weeks of chelation. Experimental endpoints were heart and liver weights, iron concentration and histology.


RESULTS
In the heart, there was no significant difference among the treatment groups for wet-to-dry ratio, iron concentration and iron content. DFX-treated animals exhibited lower organ weights relative to sham-chelated animals (less iron-mediated hypertrophy). DFO-treated organs did not differ from sham-chelated organs in any aspects. DFX significantly cleared hepatic iron. No additive effects were observed in the organs of DFO/DFX-treated animals.


CONCLUSIONS
Combined DFO/DFX therapy produced no detectable additive effect above DFX monotherapy in either the liver or heart, suggesting competition with spontaneous iron elimination mechanisms for chelatable iron. Combined therapy was well tolerated, but its efficacy could not be proven due to limitations in the animal model.
Otto-Duessel
Maya
M
Division of Pediatric Cardiology, Department of Cardiology, Children's Hospital Los Angeles, Los Angeles, Calif 90027, USA.
Brewer
Casey
C
Gonzalez
Ignacio
I
Nick
Hanspeter
H
Wood
John C
JC
D000818:Animals; D001565:Benzoates / Q000008:administration & dosage*; D000077588:Deferasirox; D003676:Deferoxamine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005849:Gerbillinae; D006321:Heart; D019190:Iron Overload / Q000188:drug therapy*; D008099:Liver; D009929:Organ Size; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
D001565:Benzoates; D014230:Triazoles; D003676:Deferoxamine; D000077588:Deferasirox