title: Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole.
abstract: OBJECTIVE
  The acid-inhibitory effect of lansoprazole depends on differences in cytochrome P450 (CYP) 2C19 genotypes. We assessed whether therapeutic effects of lansoprazole on gastroesophageal reflux disease (GERD) depended on the CYP2C19 genotype status in relation to the grade of GERD.
  
  
  METHODS
  A total of 65 patients with GERD (grades A-D) completed treatment with lansoprazole, by taking 30 mg orally once a day for 8 weeks. The CYP2C19 genotype status of patients was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Before and after treatment, esophageal endoscopy was performed. GERD was considered to be cured on the basis of endoscopic findings at the end of treatment. Plasma lansoprazole levels could be determined at 3 hours after the last 30-mg dose of lansoprazole in the 27 genotyped patients.
  
  
  RESULTS
  Cure rates for GERD depended significantly on the CYP2C19 genotype status, as well as the grade of GERD before treatment. Cure rates in the homozygous extensive, heterozygous extensive, and poor metabolizer groups were 45.8%, 67.9%, and 84.6%, respectively. Cure rates in the groups with GERD grade A, grade B, and grade C or D were 85.0%, 60.0%, and 45.0%, respectively. The cure rate in patients with the homozygous extensive metabolizer genotype of CYP2C19 with a GERD grade of C or D was very low (16.7%). Plasma lansoprazole levels in patients with the homozygous extensive metabolizer genotype were the lowest of the 3 groups.
  
  
  CONCLUSIONS
  CYP2C19 genotype status, as well as the grade of GERD before treatment, is one of the determinants for the success or failure of treatment of GERD with lansoprazole. The low cure rate in patients with the homozygous extensive metabolizer genotype appeared to be a result of these patients having the lowest plasma lansoprazole levels among the 3 genotype groups.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Japan. furutat@mail,nih.gov
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
authors.forename: Naohito
authors.initials: N
authors.lastname: Shirai
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Watanabe
authors.forename: Satoru
authors.initials: S
authors.lastname: Honda
authors.forename: Ken
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iida
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sato
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kajimura
authors.forename: Hajime
authors.initials: H
authors.lastname: Futami
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Takayanagi
authors.forename: Masami
authors.initials: M
authors.lastname: Yamada
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ohashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishizaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hanai
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D016001:Confidence Intervals; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005764:Gastroesophageal Reflux / Q000145:classification / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D005838:Genotype; D016481:Helicobacter Infections / Q000145:classification / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D016480:Helicobacter pylori; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D064747:Lansoprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole