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 UGT1A1. Results: Fifty-six patients were female, 24 were male, the great majority (88%) affected by b-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 UGT1A1*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 UGT1A1 polymorphisms and C DFX . Individual patient-tailored dosing of DFX should help to improve iron chelation efﬁcacy and to reduce dose-dependent drug toxicity.
|Titolo:||Determination of deferasirox plasma concentrations: do gender, physical and genetic differences affect chelation efficacy?|
|Data di pubblicazione:||2015|
|Appare nelle tipologie:||01.01 - Articolo su rivista|