Document Detail


Comparison of twice-daily vs once-daily deferasirox dosing in a gerbil model of iron cardiomyopathy.
MedLine Citation:
PMID:  17588475     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Despite the availability of deferoxamine chelation therapy for more than 20 years, iron cardiomyopathy remains the leading cause of death in thalassemia major patients. Effective chelation of cardiac iron is difficult; cardiac iron stores respond more slowly to chelation therapy and require a constant gradient of labile iron species between serum and myocytes. We have previously demonstrated the efficacy of once-daily deferasirox in removing previously stored cardiac iron in the gerbil, but changes in cardiac iron were relatively modest compared with hepatic iron. We postulated that daily divided dosing, by sustaining a longer labile iron gradient from myocytes to serum, would produce better cardiac iron chelation than a comparable daily dose.
METHODS: Twenty-four 8- to 10-week-old female gerbils underwent iron dextran-loading for 10 weeks, followed by a 1-week iron equilibration period. Animals were divided into three treatment groups of eight animals each and were treated with deferasirox 100 mg/kg/day as a single dose, deferasirox 100 mg/kg/day daily divided dose, or sham chelation for a total of 12 weeks. Following euthanasia, organs were harvested for quantitative iron and tissue histology.
RESULTS: Hepatic and cardiac iron contents were not statistically different between the daily single-dose and daily divided-dose groups. However, the ratio of cardiac to hepatic iron content was lower in the divided-dose group (0.78% vs 1.11%, p = 0.0007).
CONCLUSION: Daily divided dosing of deferasirox changes the relative cardiac and liver iron chelation profile compared with daily single dosing, trading improvements in cardiac iron elimination for less-effective hepatic chelation.
Authors:
Maya Otto-Duessel; Michelle Aguilar; Hanspeter Nick; Rex Moats; John C Wood
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental hematology     Volume:  35     ISSN:  0301-472X     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-25     Completed Date:  2007-08-02     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1069-73     Citation Subset:  IM    
Affiliation:
Division of Pediatric Radiology, Children's Hospital of Los Angeles, Los Angeles, CA 90027, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzoates / administration & dosage*
Cardiomyopathies / drug therapy*,  metabolism,  pathology
Disease Models, Animal*
Drug Administration Schedule
Female
Gerbillinae
Iron / metabolism
Iron Chelating Agents / administration & dosage*
Iron Overload / drug therapy*,  metabolism,  pathology
Liver / metabolism,  pathology
Myocardium / metabolism,  pathology
Triazoles / administration & dosage*
Grant Support
ID/Acronym/Agency:
1R01 HL075592-01A1/HL/NHLBI NIH HHS; M01 RR000043-475872/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Benzoates; 0/Iron Chelating Agents; 0/Triazoles; 7439-89-6/Iron; V8G4MOF2V9/deferasirox
Comments/Corrections

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