Deferasirox pharmacokinetic and toxicity correlation in β-thalassaemia major treatment.
OBJECTIVE
Deferasirox adverse effects include the following: gastrointestinal disturbance, mild elevations in serum creatinine levels and intermittent proteinuria; these events are dose-dependent and reversible with drug discontinuation, but this solution can lead to an inadequate iron chelation. For these reasons, interindividual variability of drug plasma concentration could help the clinical management of deferasirox dosage. We sought to describe deferasirox plasma exposure in a cohort of 60 adult patients.


METHODS
A fully validated chromatographic method was used to quantify deferasirox concentration in plasma collected from β-thalassaemia adult patients. Samples obtained before and after 2, 4, 6 and 24 h drug administration were evaluated. Associations between variables were tested using the Pearson test.


RESULTS
Concerning pharmacokinetic parameters, a higher interindividual variability was shown. A positive correlation was found between deferasirox area under the concentration curve over 24 h and serum creatinine (r = 0.314; P = 0.018) and between area and drug dose (r = 0.311; P = 0.016). Moreover, a negative correlation resulted among area under the concentration curve over 24 h and serum ferritin (r = -0.291; P = 0.026) and among drug half-life and its dose (r = -0.319; P = 0.013).


CONCLUSIONS
Treatment decision based on the individual characteristics could strongly contribute to minimize toxicity and increase efficacy of deferasirox therapy.
Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy.
Sarah
http://orcid.org/0000-0003-4933-0011
S
Allegra
Department of Biological and Clinical Sciences, S. Luigi Gonzaga Hospital, University of Turin, Orbassano (TO), Italy.
Silvia
S
De Francia
Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy.
Jessica
J
Cusato
Department of Biological and Clinical Sciences, S. Luigi Gonzaga Hospital, University of Turin, Orbassano (TO), Italy.
Elisa
E
Pirro
Department of Biological and Clinical Sciences, S. Luigi Gonzaga Hospital, University of Turin, Orbassano (TO), Italy.
Davide
D
Massano
Department of Biological and Clinical Sciences, S. Luigi Gonzaga Hospital, University of Turin, Orbassano (TO), Italy.
Antonio
A
Piga
Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy. antonio.davolio@unito.it.
Antonio
A
D'Avolio
D000328:Adult; D019540:Area Under Curve; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D000077588:Deferasirox; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005293:Ferritins / Q000097:blood; D006207:Half-Life; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D013056:Spectrophotometry, Ultraviolet; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D017086:beta-Thalassemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*
D001565:Benzoates; D015415:Biomarkers; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D003404:Creatinine; D000077588:Deferasirox
Exjade®; iron chelation; iron overload; thalassaemia; therapeutic drug monitoring