title: CYP2C19 genotype and pharmacokinetics of three proton pump inhibitors in healthy subjects.
abstract: OBJECTIVE
  To predict the CYP2C19 genotype-dependence in anti-Helicobacter pylori (H. pylori) therapy when lansoprazole or rabeprazole was used instead of omeprazole as a proton pump inhibitor (PPI).
  
  
  METHODS
  A comparative pharmacokinetic study with each PPI was designed as an open, randomized, and crossover study of 18 Japanese healthy volunteers who were classified into the homozygous, heterozygous extensive metabolizer and the poor metabolizer based on the CYP2C19 genotype determined by PCR-RFLP method. Each subject received a single oral dose of 20 mg omeprazole, 30 mg lansoprazole, or 20 mg sodium rabeprazole, with at least 1 week washout period between treatments. Plasma concentrations of PPIs and their metabolites were monitored until 12 h after medication.
  
  
  RESULTS
  Pharmacokinetic profiles of omeprazole and lansoprazole were well correlated with the CYP2C19 genotype. The heterozygous extensive metabolizer was slightly different from the homozygote, but there was no statistically significant difference. The CYP2C19 genotype dependence found for lansoprazole was not obvious compared with omeprazole. As for rabeprazole, the pharmacokinetic profile was independent of the CYP2C19 genotype.
  
  
  CONCLUSIONS
  CYP2C19 genotype dependence will be found in the anti-H. pylori therapy even when lansoprazole is used as the PPI.
authors.affiliation: Second Department of Internal Medicine, School of Medicine, Kobe University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sakai
authors.forename: N
authors.initials: N
authors.lastname: Aoyama
authors.forename: T
authors.initials: T
authors.lastname: Kita
authors.forename: T
authors.initials: T
authors.lastname: Sakaeda
authors.forename: K
authors.initials: K
authors.lastname: Nishiguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Nishitora
authors.forename: T
authors.initials: T
authors.lastname: Hohda
authors.forename: D
authors.initials: D
authors.lastname: Sirasaka
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: Y
authors.initials: Y
authors.lastname: Tanigawara
authors.forename: M
authors.initials: M
authors.lastname: Kasuga
authors.forename: K
authors.initials: K
authors.lastname: Okumura
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D001562:Benzimidazoles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D064747:Lansoprazole; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D054328:Proton Pump Inhibitors; D064750:Rabeprazole
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064750:Rabeprazole; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole