title: Rabeprazole 10 mg q.d.s. decreases 24-h intragastric acidity significantly more than rabeprazole 20 mg b.d. or 40 mg o.m., overcoming CYP2C19 genotype.
abstract: BACKGROUND
  Standard dosing (i.e. once daily) of proton pump inhibitors (PPIs) cannot inhibit acid secretion for a full 24 h. Better therapeutic regimens using PPIs are required to sustain potent acid inhibition for the full 24 h in all patients with acid-related diseases.
  
  
  OBJECTIVE
  To evaluate acid inhibitory effects by different dosing times of a PPI at the same daily dosage, in a study involving 70 rounds of pH monitoring.
  
  
  METHODS
  Using pH monitoring, we evaluated the efficacy of different divided treatment regimens with the same total daily dose of rabeprazole (40 mg o.m., 15 rounds; 20 mg b.d., 20 rounds; 10 mg q.d.s., 35 rounds) on day 7 or 8 of PPI dosing.
  
  
  RESULTS
  In the study of divided treatment, the median pH (when administered once, twice or four times to achieve a daily dose of 40 mg) was 4.8 (3.6-6.4), 5.7 (4.1-7.4), 6.6 (4.9-8.4), respectively. When comparing the median pHs at the same CYP2C19 genotype among different dosing times of rabeprazole, the median pH attained with 10 mg q.d.s. was significantly higher than that in 40 mg o.m. or 20 mg b.d. Increase in the frequency of dosing effectively increased pH [median percent time of pH > 4.0 with q.d.s. therapy: 95.5% (63.2-100.0%)], irrespective to CYP2C19 genotype.
  
  
  CONCLUSIONS
  Four times daily dosing with rabeprazole 10 mg achieved potent acid inhibition, including during the night-time, suggesting its potential usefulness as a regimen for patients who are refractory to standard once daily PPI treatment.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan. mitsu@hama-med.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Sugimoto
authors.forename: N
authors.initials: N
authors.lastname: Shirai
authors.forename: M
authors.initials: M
authors.lastname: Nishino
authors.forename: C
authors.initials: C
authors.lastname: Kodaira
authors.forename: T
authors.initials: T
authors.lastname: Uotani
authors.forename: M
authors.initials: M
authors.lastname: Yamade
authors.forename: S
authors.initials: S
authors.lastname: Sahara
authors.forename: H
authors.initials: H
authors.lastname: Ichikawa
authors.forename: K
authors.initials: K
authors.lastname: Sugimoto
authors.forename: H
authors.initials: H
authors.lastname: Miyajima
authors.forename: T
authors.initials: T
authors.lastname: Furuta
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage*; D000284:Administration, Oral; D000293:Adolescent; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005838:Genotype; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011110:Polymorphism, Genetic / Q000187:drug effects; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D064750:Rabeprazole; D013997:Time Factors; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19