title: Role of pharmacogenetics on deferasirox AUC and efficacy.
abstract: We evaluated deferasirox pharmacokinetic according to SNPs in genes involved in its metabolism and elimination. Moreover, we defined a plasma area under the curve cut-off value predicting therapy response.
  
  
  
  Allelic discrimination was performed by real-time PCR. Drug plasma concentrations were measured by a high performance liquid chromatography system coupled with an ultraviolet method.
  
  
  
  Pharmacokinetic parameters were significantly influenced by UGT1A1 rs887829C>T, UGT1A3 rs1983023C>T and rs3806596A>G SNPs. Area under the curve cut-off values of 360 μg/ml/h for efficacy were here defined and 250 μg/ml/h for nonresponse was reported. UGT1A3 rs3806596GG and ABCG2 rs13120400CC genotypes were factors able to predict efficacy, whereas UGT1A3 rs3806596GG was a nonresponse predictor.
  
  
  
  These data show how screening patient's genetic profile may help clinicians to optimize iron chelation therapy with deferasirox.
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cusato
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Allegra
authors.affiliation: Department of Biological & Clinical Sciences, University of Turin, S. Luigi Gonzaga Hospital, 10043 Orbassano (TO), Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: De Francia
authors.affiliation: Department of Pediatrics, Centre for Microcitemie, University of Turin, S. Luigi Gonzaga Hospital, 10043 Orbassano (TO), Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Massano
authors.affiliation: Department of Pediatrics, Centre for Microcitemie, University of Turin, S. Luigi Gonzaga Hospital, 10043 Orbassano (TO), Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Piga
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy.|Laboratory of Clinical Pharmacology & Pharmacogenetics, Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Corso Svizzera 164-10149 Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
mesh_terms: D000328:Adult; D000483:Alleles; D019540:Area Under Curve; D001565:Benzoates / Q000097:blood* / Q000493:pharmacokinetics*; D015331:Cohort Studies; D000077588:Deferasirox; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014230:Triazoles / Q000097:blood* / Q000493:pharmacokinetics*; D000099148:UGT1A1 Enzyme
chemical_list: D001565:Benzoates; D000077588:Deferasirox; D014453:Glucuronosyltransferase; D014230:Triazoles; D000099148:UGT1A1 Enzyme; C122075:UDP-glucuronosyltransferase, UGT1A3
keywords: ABCG2; SNPs; UGT1A1; UGT1A3; iron overload; pharmacokinetics