title: Plasma concentration of rabeprazole after 8-week administration in gastroesophageal reflux disease patients and intragastric pH elevation.
abstract: OBJECTIVE
  The plasma concentration of rabeprazole in patients treated for gastroesophageal reflux disease (GERD) has not been reported, although the concentration in healthy volunteers has been reported previously. Here, CYP2C19 genotype effects of rabeprazole on the area under the plasma concentration-time curve (AUC) and the pH elevation were studied in GERD patients.
  
  
  METHODS
  Rabeprazole 10 mg/day was administrated for 8 weeks. AUC of rabeprazole in 18 Helicobacter pylori-negative GERD subjects (five CYP2C19 homozygous extensive metabolizers [homEM], eight heterozygous extensive metabolizers [hetEM] and five poor metabolizers [PM]) were determined after the final medication. Intragastric pH was recorded for 24 h at baseline and after the final medication.
  
  
  RESULTS
  The AUC in the PM group (957 ng x h/mL) was significantly higher than those of homEM (375 ng x h/mL) and hetEM (542 ng x h/mL) groups. Median 24-h pH curves, median 24-h pH values and 24-h and nocturnal pH > 4 and pH > 3 holding times did not significantly differ among these groups. Disappearance of erosive lesions was observed after the treatment in all subjects with grade A, B or C at baseline irrespective of CYP2C19 genotypes.
  
  
  CONCLUSIONS
  The AUC of rabeprazole depended on the CYP2C19 genotypes in Japanese GERD patients; however, the intragastric pH elevation was independent of CYP2C19 genotypes, which is consistent with the CYP2C19 genotype-independent healing efficacy of erosive lesions by rabeprazole. The present low AUC values indicated that abnormal accumulative effects on AUC did not occur during the period of the 8-week administration of rabeprazole.
authors.affiliation: Department of Gastroenterology, Akita Red Cross Hospital, Akita, Japan. h-yamano@h9.dion.ne.jp
authors.forename: Hiro-o
authors.initials: HO
authors.lastname: Yamano
authors.forename: Hiro-o
authors.initials: HO
authors.lastname: Matsushita
authors.forename: Seiko
authors.initials: S
authors.lastname: Yanagiwara
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D005745:Gastric Acidity Determination; D005764:Gastroesophageal Reflux / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008875:Middle Aged; D011110:Polymorphism, Genetic; D064750:Rabeprazole; D013997:Time Factors
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D064750:Rabeprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19