title: Influence of the CYP2B6 polymorphism on the pharmacokinetics of mitotane.
abstract: OBJECTIVE
  The aim of this study was to assess the potential impact of the pharmacogenetic variability of CYP2B6 and ABCB1 genes on the pharmacokinetics of mitotane.
  
  
  METHODS
  A retrospective analysis was carried out on 27 patients with adrenocortical carcinoma on postoperative adjunctive mitotane. CYP2B6 and ABCB1 polymorphisms were genotyped and tested for an association with plasma trough concentration after 3, 6, 9, and 12 months of therapy.
  
  
  RESULTS
  Patients with the GT/TT genotype had higher mitotane plasma concentrations compared with patients with GG at 3 months (14.80 vs. 8.01 μg/ml; P=0.008) and 6 months (17.70 vs. 9.75 μg/ml; P=0.015). Multivariate logistic regression analysis showed that only the CYP2B6 rs3745274GT/TT genotype (odds ratio=10.7; P=0.017) was a predictor of mitotane plasma concentrations of at least 14 µg/ml after 3 months of treatment. Mitotane concentrations were not influenced by the polymorphisms of the ABCB1 gene.
  
  
  CONCLUSIONS
  Evaluation of the CYP2B6 polymorphism enabled prediction of the individual response to adjuvant mitotane treatment.
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy. antonio.davolio@unito.it
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.forename: Silvia
authors.initials: S
authors.lastname: De Francia
authors.forename: Vittoria
authors.initials: V
authors.lastname: Basile
authors.forename: Jessica
authors.initials: J
authors.lastname: Cusato
authors.forename: Francesca
authors.initials: F
authors.lastname: De Martino
authors.forename: Elisa
authors.initials: E
authors.lastname: Pirro
authors.forename: Francesca
authors.initials: F
authors.lastname: Piccione
authors.forename: Arianna
authors.initials: A
authors.lastname: Ardito
authors.forename: Barbara
authors.initials: B
authors.lastname: Zaggia
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065702:Cytochrome P-450 CYP2B6; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008939:Mitotane; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6