title: Effect of increasing esomeprazole and pantoprazole doses on acid control in patients with symptoms of gastro-oesophageal reflux disease: a randomized, dose-response study.
abstract: OBJECTIVE
  In patients with gastro-oesophageal reflux disease (GORD), dose escalation or drug switching may be considered in those with symptoms that persist despite standard-dose proton pump inhibitor (PPI) therapy. This study set out to assess whether increasing the dosage of oral esomeprazole and pantoprazole improves acid control in GORD patients, and to compare the pharmacodynamic efficacy of esomeprazole and pantoprazole administered at different dosages.
  
  
  METHODS
  This was an open-label, randomized, six-way crossover study that included Helicobacter pylori-negative GORD patients (aged 20-60 years) with <30% of time with intragastric pH>4. Patients were treated with oral once-daily esomeprazole 20 mg, 40 mg and 80 mg, and pantoprazole 20 mg, 40 mg and 80 mg, for 5 days. The main outcome measures were time with intragastric pH>4 over 24 hours, median pH over 24 hours and area under the hydrogen ion versus time curve on day 5 for each treatment period.
  
  
  RESULTS
  Dose escalation with both PPIs improved acid control. The proportion of time with intragastric pH>4 (day 5) was 46.7% with esomeprazole 20 mg/day, 58.6% with esomeprazole 40 mg/day, and 65.8% with esomeprazole 80 mg/day; the corresponding percentages with pantoprazole were 28.6%, 36.9% and 44.9%, respectively. On a milligram-per-milligram basis, esomeprazole provided greater acid control than pantoprazole (p<0.001).
  
  
  CONCLUSIONS
  Dose escalation with oral esomeprazole and pantoprazole improves acid control in patients with GORD, although esomeprazole provides significantly greater acid control on a milligram-per-milligram basis.
authors.affiliation: Brain-Gut Research Group, Gastroenterology Group Practice, Berne, Switzerland. cws@ggp.ch
authors.forename: Clive
authors.initials: C
authors.lastname: Wilder-Smith
authors.forename: Anna
authors.initials: A
authors.lastname: Backlund
authors.forename: Göran
authors.initials: G
authors.lastname: Eckerwall
authors.forename: Tore
authors.initials: T
authors.lastname: Lind
authors.forename: Mia
authors.initials: M
authors.lastname: Fjellman
authors.forename: Kerstin
authors.initials: K
authors.lastname: Röhss
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use*; D000328:Adult; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D064098:Esomeprazole / Q000627:therapeutic use*; D005260:Female; D005745:Gastric Acidity Determination; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077402:Pantoprazole
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D000077402:Pantoprazole; D064098:Esomeprazole