title: Initial 48-hour acid inhibition by intravenous infusion of omeprazole, famotidine, or both in relation to cytochrome P450 2C19 genotype status.
abstract: OBJECTIVE
  Faster and stronger acid inhibition is required for the treatment of hemorrhage from peptic ulcers. We compared the effects of intravenous infusion regimens of a proton pump inhibitor (PPI) alone, a histamine 2 receptor antagonist (H2RA) alone, and the combination of a PPI with an H2RA on acid inhibition in the early postadministration phase in relation to cytochrome P450 (CYP) 2C19 genotype status.
  
  
  METHODS
  Fifteen Helicobacter pylori-positive volunteers with 3 different CYP2C19 genotypes were administered twice-daily intravenous infusions of 20 mg famotidine alone, 20 mg omeprazole alone, 10 mg omeprazole plus 10 mg famotidine (half-concomitant regimen), and 20 mg omeprazole plus 20 mg famotidine (full-concomitant regimen) for 2 days. The subjects underwent 48-hour intragastric pH monitoring.
  
  
  RESULTS
  In homozygous extensive metabolizers (EMs) the median first 24-hour intragastric pH with the full-concomitant regimen was 4.8 (range, 4.5-5.4), which was significantly higher than that with omeprazole alone (3.9 [range, 2.6-4.7], P=.043) or famotidine alone (4.4 [range, 3.8-4.9], P=.043). In heterozygous EMs and poor metabolizers the respective median first 24-hour pH values attained with omeprazole alone (5.8 [range, 4.3-6.3] and 6.1 [range, 5.3-7.4]) and the full-concomitant regimen (5.8 [range, 5.1-6.4] and 5.8 [range, 5.4-6.2]) were significantly higher than those attained with famotidine alone (4.1 [range, 3.9-6.5] and 4.7 [range, 3.7-5.7], P=.043 for all).
  
  
  CONCLUSIONS
  For faster and stronger acid inhibition, the concomitant infusion regimen of a PPI and an H2RA appears to be therapeutically useful in homozygous and heterozygous EMs, but omeprazole alone appears to be sufficient in poor metabolizers of CYP2C19.
authors.affiliation: First Department of Medicine and Center for Clinical Research, Hamamatsu University School of Medicine, Shizuoka, Japan. mitsu@hama-med.ac.jp
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
authors.forename: Naohito
authors.initials: N
authors.lastname: Shirai
authors.forename: Mutsuhiro
authors.initials: M
authors.lastname: Ikuma
authors.forename: Akira
authors.initials: A
authors.lastname: Hishida
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishizaki
mesh_terms: D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D015738:Famotidine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005745:Gastric Acidity Determination; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics; D016480:Helicobacter pylori / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016037:Single-Blind Method; D013997:Time Factors
chemical_list: D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D015738:Famotidine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole