title: Deferasirox pharmacogenetic influence on pharmacokinetic, efficacy and toxicity in a cohort of pediatric patients.
abstract: OBJECTIVE
  We aimed to evaluate the influence of genetic polymorphisms involved in deferasirox metabolism and transport on its pharmacokinetics and treatment toxicity, in a cohort of β-thalassaemic children.
  
  
  METHODS
  Drug plasma concentrations were measured by a HPLC-UV method. Allelic discrimination for UGT1A1, UGT1A3, CYP1A1, CYP1A2, CYP2D6, MRP2 and BCRP1 polymorphisms was performed by real-time PCR.
  
  
  RESULTS
  CYP1A1 rs2606345AA influenced Ctrough(p = 0.001) and t1/2(p = 0.042), CYP1A1 rs4646903TC/CC (p = 0.005) and BCRP1 rs2231142GA/AA (p = 0.005) influenced Tmaxand CYP2D6 rs1135840CG/GG influenced Cmax(p = 0.044). UGT1A1 rs887829TT (p = 0.002) and CYP1A2 rs762551CC (p = 0.019) resulted as predictive factor of ferritin levels and CYP1A1 rs2606345CA/AA (p = 0.021) and CYP1A2 rs762551AC/CC (p = 0.027) of liver iron concentration.
  
  
  CONCLUSIONS
  Our data suggest the usefulness of deferasirox pharmacogenetics in pediatric treatment optimization.
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Allegra
authors.affiliation: Department of Biological & Clinical Sciences, S Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano (TO), Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: De Francia
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cusato
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, 10149 Turin, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Arduino
authors.affiliation: Department of Biological & Clinical Sciences, S Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano (TO), Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Massano
authors.affiliation: Department of Biological & Clinical Sciences, S Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano (TO), Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Longo
authors.affiliation: Department of Biological & Clinical Sciences, S Luigi Gonzaga Hospital, University of Turin, 10043 Orbassano (TO), 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, 10149 Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
mesh_terms: D000293:Adolescent; D001565:Benzoates / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D000077588:Deferasirox; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D014230:Triazoles / Q000097:blood / Q000627:therapeutic use / Q000633:toxicity; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox
keywords: BCRP1; CYP1A1; CYP1A2; CYP2D6; LIC; SNP; creatinine; ferritin; iron overload; β-thalassemia