title: Comparison of acid inhibition with standard dosages of proton pump inhibitors in relation to CYP2C19 genotype in Japanese.
abstract: BACKGROUND
  The aim of therapeutic regimens using proton pump inhibitors (PPIs) in patients with acid-related diseases is to potently inhibit acid secretion for the full 24 h. However, optimum treatment is still unclear because the pharmacodynamics of PPIs differ among CYP2C19 genotypes and most of the previous studies have had loss of sample power.
  
  
  METHODS
  Using pH monitoring, we compared acid inhibition at standard dosage of omeprazole (20 mg, 50 times), lansoprazole (30 mg, 68 times), and rabeprazole (10 mg, 65 times) in Helicobacter pylori-negative healthy young Japanese volunteers.
  
  
  RESULTS
  Median pH with rabeprazole was 5.4 (3.3-7.5), which was significantly greater than with either omeprazole [4.4 (2.1-7.3)] or lansoprazole [4.8 (3.5-6.4)] (both P < 0.05). Median 24-h pH differed among the different CYP2C19 genotypes in all three PPIs. In CYP2C19 extensive metabolizers (EMs), the genotype that is refractory to PPI treatment, median pH with omeprazole, lansoprazole, and rabeprazole was 3.8 (2.1-4.4), 4.5 (3.5-5.3) and 4.8 (3.3-7.5), respectively.
  
  
  CONCLUSIONS
  Treatment with the selected PPIs at their standard dosages had difficulty maintaining acid inhibition for a full 24 h, especially in CYP2C19 EM. However, rabeprazole has the merit of less influence of CYP2C19 genotype compared with the other PPIs.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan, mitsu@hama-med.ac.jp.
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Naohito
authors.initials: N
authors.lastname: Shirai
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nishino
authors.forename: Chise
authors.initials: C
authors.lastname: Kodaira
authors.forename: Takahiro
authors.initials: T
authors.lastname: Uotani
authors.forename: Shu
authors.initials: S
authors.lastname: Sahara
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Takuma
authors.initials: T
authors.lastname: Kagami
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration; D064747:Lansoprazole / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D064750:Rabeprazole / Q000494:pharmacology; D055815:Young Adult
chemical_list: D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064750:Rabeprazole; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole