Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring
Abstract Deferasirox (DFX) is the newest among three different chelators available to treat iron overload in iron-loading anaemias, firstly released as Dispersible Tablets (DT) and more recently replaced by Film-Coated Tablets (FCT). In this retrospective observational study, pharmacokinetics, pharm...
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doaj-5ec962bf5733487bb7ac0972af87b9732021-06-20T11:32:44ZengNature Publishing GroupScientific Reports2045-23222021-06-0111111210.1038/s41598-021-91983-wPharmacological and clinical evaluation of deferasirox formulations for treatment tailoringAndrea Piolatto0Paola Berchialla1Sarah Allegra2Silvia De Francia3Giovanni Battista Ferrero4Antonio Piga5Filomena Longo6Department of Clinical and Biological Sciences, University of TorinoDepartment of Clinical and Biological Sciences, University of TorinoClinical Pharmacology, Department of Clinical and Biological Sciences, University of TorinoClinical Pharmacology, Department of Clinical and Biological Sciences, University of TorinoDepartment of Clinical and Biological Sciences, University of TorinoDepartment of Clinical and Biological Sciences, University of TorinoDepartment of Clinical and Biological Sciences, University of TorinoAbstract Deferasirox (DFX) is the newest among three different chelators available to treat iron overload in iron-loading anaemias, firstly released as Dispersible Tablets (DT) and more recently replaced by Film-Coated Tablets (FCT). In this retrospective observational study, pharmacokinetics, pharmacodynamics, and safety features of DFX treatment were analyzed in 74 patients that took both formulations subsequently under clinical practice conditions. Bioavailability of DFX FCT compared to DT resulted higher than expected [Cmax: 99.5 (FCT) and 69.7 (DT) μMol/L; AUC: 1278 (FCT) and 846 (DT), P < 0.0001]. DFX FCT was also superior in scalability among doses. After one year of treatment for each formulation, no differences were observed between the treatments in the overall iron overload levels; however, DFX FCT but not DT showed a significant dose–response correlation [Spearman r (dose-serum ferritin variation): − 0.54, P < 0.0001]. Despite being administered at different dosages, the long-term safety profile was not different between formulations: a significant increase in renal impairment risk was observed for both treatments and it was reversible under strict monitoring (P < 0.002). Altogether, these data constitute a comprehensive comparison of DFX formulations in thalassaemia and other iron-loading anaemias, confirming the effectiveness and safety characteristics of DFX and its applicability for treatment tailoring.https://doi.org/10.1038/s41598-021-91983-w |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrea Piolatto Paola Berchialla Sarah Allegra Silvia De Francia Giovanni Battista Ferrero Antonio Piga Filomena Longo |
spellingShingle |
Andrea Piolatto Paola Berchialla Sarah Allegra Silvia De Francia Giovanni Battista Ferrero Antonio Piga Filomena Longo Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring Scientific Reports |
author_facet |
Andrea Piolatto Paola Berchialla Sarah Allegra Silvia De Francia Giovanni Battista Ferrero Antonio Piga Filomena Longo |
author_sort |
Andrea Piolatto |
title |
Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring |
title_short |
Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring |
title_full |
Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring |
title_fullStr |
Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring |
title_full_unstemmed |
Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring |
title_sort |
pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-06-01 |
description |
Abstract Deferasirox (DFX) is the newest among three different chelators available to treat iron overload in iron-loading anaemias, firstly released as Dispersible Tablets (DT) and more recently replaced by Film-Coated Tablets (FCT). In this retrospective observational study, pharmacokinetics, pharmacodynamics, and safety features of DFX treatment were analyzed in 74 patients that took both formulations subsequently under clinical practice conditions. Bioavailability of DFX FCT compared to DT resulted higher than expected [Cmax: 99.5 (FCT) and 69.7 (DT) μMol/L; AUC: 1278 (FCT) and 846 (DT), P < 0.0001]. DFX FCT was also superior in scalability among doses. After one year of treatment for each formulation, no differences were observed between the treatments in the overall iron overload levels; however, DFX FCT but not DT showed a significant dose–response correlation [Spearman r (dose-serum ferritin variation): − 0.54, P < 0.0001]. Despite being administered at different dosages, the long-term safety profile was not different between formulations: a significant increase in renal impairment risk was observed for both treatments and it was reversible under strict monitoring (P < 0.002). Altogether, these data constitute a comprehensive comparison of DFX formulations in thalassaemia and other iron-loading anaemias, confirming the effectiveness and safety characteristics of DFX and its applicability for treatment tailoring. |
url |
https://doi.org/10.1038/s41598-021-91983-w |
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