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Determination of deferasirox plasma concentrations: do gender, physical and genetic differences affect chelation efficacy?
Author(s) -
Mattioli Francesca,
Puntoni Matteo,
Marini Valeria,
Fucile Carmen,
Milano Giulia,
Robbiano Luigi,
Perrotta Silverio,
Pinto Valeria,
Martelli Antonietta,
Forni Gian Luca
Publication year - 2015
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12419
Subject(s) - deferasirox , medicine , univariate analysis , pharmacokinetics , multivariate analysis , ferritin , thalassemia , gastroenterology
Objectives Bioavailability of deferasirox ( DFX ) is significantly affected by the timing of administration relative to times and to composition of meals. Its elimination half‐life is also highly variable – in some patients as a result of gene polymorphisms. Understanding whether deferasirox plasma levels are related to specific characteristics of patients could help physicians to devise a drug regimen tailored the individual patient. Methods We analyzed deferasirox plasma concentrations ( C DFX ) in 80 patients with transfusion‐dependent anemias, such as thalassemia, by a high performance liquid chromatography ( HPLC ) assay. We used a multivariate linear regression model to find significant associations between C DFX and clinical/demographical characteristics of patients. All patients were genotyped for UGT 1A1 . Results Fifty‐six patients were female, 24 were male, the great majority (88%) affected by β ‐thalassemia, and 15 were children and adolescents. No statistical correlation was detectable between C DFX and DFX dose ( P = 0.6). Age, time from last drug intake to blood sampling, and ferritin levels in the 6 months before study initiation were significantly and inversely associated with C DFX in univariate analysis. In the multivariate analysis, the only two factors independently and inversely associated with C DFX levels were time from last drug intake to blood sampling and ferritin levels ( P = 0.006). A significant inverse correlation ( P = 0.03) was observed between C DFX and UGT 1A1*28 gene polymorphism, but only in patients with levels of lean body mass ( LBM ) below the median ( P for interaction = 0.05). Conclusions The results could indicate that a higher plasma DFX concentration could be associated with greater chelation efficacy. As a correlation between dose and C DFX was not demonstrated, it seems useful to monitor the concentrations to optimize and determine the most appropriate dose for each patient. Interesting results emerged from the analysis of genetic and physical characteristics of patients: LBM was a borderline significant effect modifier of the relationship between UGT 1A1 polymorphisms and C DFX . Individual patient‐tailored dosing of DFX should help to improve iron chelation efficacy and to reduce dose‐dependent drug toxicity.