title: Association of ABCB1 polymorphisms with erlotinib pharmacokinetics and toxicity in Japanese patients with non-small-cell lung cancer.
abstract: OBJECTIVE
  We analyzed the association of ABCB1 polymorphisms with erlotinib-induced toxicity and the pharmacokinetics in patients with non-small-cell lung cancer.
  
  
  METHODS
  After erlotinib 150 mg was administered to 50 patients, ABCB1 polymorphisms were analyzed via either TaqMan(®) assays or direct nucleotide sequencing. Plasma concentrations were measured by HPLC.
  
  
  RESULTS
  The trough concentration at steady state in patients with the ABCB1 1236TT-2677TT-3435TT genotype was higher compared with others groups (p = 0.021) and patients carrying this genotype had a higher risk of developing higher grade 2 toxicity (p = 0.012).
  
  
  CONCLUSIONS
  The present study suggested that the ABCB1 1236TT-2677TT-3435TT genotype was associated with higher plasma concentration and the risk of developing higher toxicity in patients treated with erlotinib.
authors.affiliation: Kumamoto University Hospital, Kumamoto, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hamada
authors.forename: Ji-Ichiro
authors.initials: J
authors.lastname: Sasaki
authors.forename: Sho
authors.initials: S
authors.lastname: Saeki
authors.forename: Norihiro
authors.initials: N
authors.lastname: Iwamoto
authors.forename: Megumi
authors.initials: M
authors.lastname: Inaba
authors.forename: Sunao
authors.initials: S
authors.lastname: Ushijima
authors.forename: Maki
authors.initials: M
authors.lastname: Urata
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kishi
authors.forename: Shinji
authors.initials: S
authors.lastname: Fujii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Semba
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kashiwabara
authors.forename: Yukari
authors.initials: Y
authors.lastname: Tsubata
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Isobe
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kohrogi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saito
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors