title: Effect of CYP2C19 polymorphism on the safety and efficacy of omeprazole in Japanese patients with recurrent reflux oesophagitis.
abstract: BACKGROUND
  The polymorphic enzyme cytochrome P450 2C19 affects omeprazole metabolism. This influence on metabolism might affect serum gastrin levels, and safety, during long-term treatment of reflux oesophagitis.
  
  
  OBJECTIVE
  To examine the relationship between cytochrome P450 2C19 genotype and the safety profile of long-term omeprazole treatment.
  
  
  METHODS
  A total of 119 Japanese patients with recurrent reflux oesophagitis underwent cytochrome P450 2C19 genotyping prior to receiving daily omeprazole 10 mg or 20 mg for 6-12 months, during which adverse event frequency, serum gastrin levels and endoscopic findings were monitored.
  
  
  RESULTS
  The incidences of adverse events, serious adverse events and adverse events leading to withdrawal did not differ between homozygous extensive metabolizer (n = 46), heterozygous extensive metabolizer (n = 53) or poor metabolizer (n = 20) groups. In all genotype groups, serum gastrin increased during the first 3 months of dosing but stabilized thereafter. No significant differences were seen either in the rate of reflux oesophagitis healing or symptom improvement among genotype groups.
  
  
  CONCLUSIONS
  Long-term treatment with omeprazole was well-tolerated in Japanese patients, irrespective of their cytochrome P450 2C19 metabolic genotype, indicating that dose adjustment depending on metabolic genotype is not required during treatment with omeprazole.
authors.affiliation: Juntendo University School of Medicine, Hongo, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohkusa
authors.forename: T
authors.initials: T
authors.lastname: Maekawa
authors.forename: T
authors.initials: T
authors.lastname: Arakawa
authors.forename: M
authors.initials: M
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: E
authors.initials: E
authors.lastname: Hoshino
authors.forename: Y
authors.initials: Y
authors.lastname: Mitachi
authors.forename: S
authors.initials: S
authors.lastname: Hamada
authors.forename: T
authors.initials: T
authors.lastname: Mine
authors.forename: Y
authors.initials: Y
authors.lastname: Kawahara
authors.forename: T
authors.initials: T
authors.lastname: Nagai
authors.forename: N
authors.initials: N
authors.lastname: Aoyama
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Tadokoro
authors.forename: N
authors.initials: N
authors.lastname: Chida
authors.forename: Y
authors.initials: Y
authors.lastname: Konda
authors.forename: H
authors.initials: H
authors.lastname: Seno
authors.forename: T
authors.initials: T
authors.lastname: Shimatani
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: N
authors.initials: N
authors.lastname: Sato
mesh_terms: D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D004942:Esophagitis, Peptic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005755:Gastrins / Q000097:blood; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009853:Omeprazole / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000897:Anti-Ulcer Agents; D005755:Gastrins; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole