title: One-day front-loading with four doses of rabeprazole followed by a standard twice-daily regimen provides sufficient acid inhibition in extensive metabolizers of CYP2C19.
abstract: BACKGROUND
  Four times daily dosing (qid) with a proton pump inhibitor can cause rapid increase in intragastric pH. We investigated the efficacy of the front-loading with rabeprazole 10 mg qid on a subsequent regimen with rabeprazole 10 mg twice daily (bid) for 7 days in extensive metabolizers (EMs) of CYP2C19.
  
  
  METHODS
  Five EMs received three different 1-week regimens in a crossover manner as follows: (1) rabeprazole 10 mg bid for 7 days; (2) a front-loading regimen of rabeprazole (rabeprazole 10 mg qid on day 0 and bid on days 1 to 7); and (3) rabeprazole 10 mg qid for 7 days. Five intermediate metabolizers (IMs) and four poor metabolizers (PMs) received rabeprazole 10 mg bid regimen only. Twenty-four-hour intragastric pH-monitorings were performed on days 1, 4, and 7. Area under the intragastric pH-time curves (AUCs) from days 1 to 7 was calculated using 24-h median intragastric pHs on days 1, 4, and 7.
  
  
  RESULTS
  Twenty-four-hour intragastric pHs in the front-loading group on days 1, 4, and 7 were 5.1, 4.9, and 5.1, respectively. The median AUC with front-loading in EMs (34.4, pH·day) was significantly higher than that in EMs with rabeprazole 10 mg bid (30.74, p = 0.043). No statistically significant differences in median AUCs were noted among front-loading in EMs, rabeprazole 10 mg qid in EMs (37.2), rabeprazole 10 mg bid in IMs (37.3), and PMs (39.4).
  
  
  CONCLUSIONS
  The one-day front-loading regimen of rabeprazole 10 mg qid provided sufficient acid inhibition for 7 days, even in CYP2C19 EMs.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Kagami
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Mitsushige
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ichikawa
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Sahara
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Uotani
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Yamade
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hamaya
authors.affiliation: Department of Clinical Oncology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Moriya
authors.initials: M
authors.lastname: Iwaizumi
authors.affiliation: Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Osawa
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
authors.affiliation: Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan. furuta@hama-med.ac.jp.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
mesh_terms: D000293:Adolescent; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004334:Drug Administration Schedule; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D006801:Humans; D008297:Male; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D064750:Rabeprazole / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D065731:Cytochrome P-450 CYP2C19
keywords: CYP2C19; Intragastric pH; Proton pump inhibitor; Rabeprazole