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Comparison of twice-daily vs once-daily deferasirox dosing in a gerbil model of iron cardiomyopathy.
Otto-Duessel, Maya; Aguilar, Michelle; Nick, Hanspeter; Moats, Rex; Wood, John C.
Affiliation
  • Otto-Duessel M; Division of Pediatric Radiology, Children's Hospital of Los Angeles, Los Angeles, CA 90027, USA.
Exp Hematol ; 35(7): 1069-73, 2007 Jul.
Article de En | MEDLINE | ID: mdl-17588475
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.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Triazoles / Benzoates / Agents chélateurs du fer / Surcharge en fer / Modèles animaux de maladie humaine / Cardiomyopathies Limites: Animals Langue: En Journal: Exp Hematol Année: 2007 Type de document: Article Pays d'affiliation: États-Unis d'Amérique Pays de publication: Pays-Bas

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Triazoles / Benzoates / Agents chélateurs du fer / Surcharge en fer / Modèles animaux de maladie humaine / Cardiomyopathies Limites: Animals Langue: En Journal: Exp Hematol Année: 2007 Type de document: Article Pays d'affiliation: États-Unis d'Amérique Pays de publication: Pays-Bas