Deferasirox pharmacokinetic evaluation in β-thalassaemia paediatric patients

J Pharm Pharmacol. 2017 May;69(5):525-528. doi: 10.1111/jphp.12559. Epub 2016 May 27.

Abstract

Objectives: 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.

Key findings: 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.

Keywords: AUC; iron chelator; iron overload; transfusion; β-thalassaemia.

MeSH terms

  • Adolescent
  • Benzoates / pharmacokinetics*
  • Benzoates / therapeutic use*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Deferasirox
  • Female
  • Humans
  • Iron / metabolism
  • Iron Chelating Agents / pharmacokinetics*
  • Iron Chelating Agents / therapeutic use*
  • Iron Overload / drug therapy
  • Iron Overload / metabolism
  • Male
  • Treatment Outcome
  • Triazoles / pharmacokinetics*
  • Triazoles / therapeutic use*
  • beta-Thalassemia / drug therapy*
  • beta-Thalassemia / metabolism*

Substances

  • Benzoates
  • Iron Chelating Agents
  • Triazoles
  • Iron
  • Deferasirox