title: Deferasirox pharmacokinetic evaluation in β-thalassaemia paediatric patients.
abstract: OBJECTIVE
  Iron chelation in the transfusion-dependent anaemias management is essential to prevent end-organ damage and to improve survival. Deferasirox is a once-daily orally active tridentate selective iron chelator which pharmacokinetic disposition could influence treatment efficacy and toxicity. Therapeutic drug monitoring is an important tool for optimizing drug utilization and doses.
  
  
  METHODS
  A fully validated chromatographic method was used to quantify deferasirox concentration in plasma collected from paediatric patients with β-thalassaemia. Samples obtained after 5 days of washout or in naïve patients before and after 2, 4, 6 and 24 h drug administration were evaluated.
  
  
  RESULTS
  Associations between variables were tested using the Pearson test. Twenty paediatric patients were enrolled; they were mainly men (13.65%), with median age of 6.35 years and body mass index of 15.45 kg/m2. Concerning pharmacokinetic parameters, a higher interindividual variability was shown. A positive, but not significant, correlation (r = 0.363; P = 0.115) was found between deferasirox area under the concentration curve over 24 h (AUC) and drug dose.
  
  
  CONCLUSIONS
  Monitoring plasma deferasirox concentrations appears beneficial for guiding appropriate patient treatment, enhancing effectiveness and minimizing toxicity.
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy.
authors.forename: Sarah
authors.identifier: http://orcid.org/0000-0003-4933-0011
authors.initials: S
authors.lastname: Allegra
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cusato
authors.affiliation: Department of Biological and Clinical Sciences, S. Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: De Francia
authors.affiliation: Department of Biological and Clinical Sciences, S. Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pirro
authors.affiliation: Department of Pediatrics, Centre for Microcitemie, S. Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Massano
authors.affiliation: Department of Pediatrics, Centre for Microcitemie, S. Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Piga
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
mesh_terms: D000293:Adolescent; D001565:Benzoates / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D000077588:Deferasirox; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D016896:Treatment Outcome; D014230:Triazoles / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D000077588:Deferasirox
keywords: 
  AUC
  ; iron chelator; iron overload; transfusion; β-thalassaemia