title: A dose-ranging study of ranitidine and its effect on intragastric and intra-oesophageal acidity in subjects with gastro-oesophageal reflux disease.
abstract: METHODS
  This randomized, double-blind, single-centre, crossover study was designed to assess the effects of three regimens of ranitidine (150 mg b.d., 300 mg b.d. and 300 mg q.d.s.) and placebo on intra-oesophageal and intragastric pH in subjects with gastro-oesophageal reflux disease (GERD). Twenty-six subjects were screened, and 9 were evaluable by the admission criteria. These 9 subjects received each of the regimens for 72 h, and a wash-out period of at least 48 h followed each dosing period. Standard meals and beverages were provided.
  
  
  RESULTS
  With increasing doses of ranitidine, 24-h intragastric mean H+ and integrated H+ fell, and the percentage of the time the pH was equal to or greater than 4 (% time pH > or = 4) rose: the minimum effective dose for these effects was ranitidine 300 mg daily. With increasing doses of ranitidine there was also a progressive decline in mean 24-h intra-oesophageal H+ and integrated H+, and increasing % time pH > or = 4. The minimal effective dose was 300 mg daily for intra-oesophageal mean H+ and integrated H+, and 600 mg for % time pH > or = 4. The minimal effective dose to decrease the number of reflex episodes was 1200 mg ranitidine. For the daytime upright position, a dose effect of increasing ranitidine was also seen, with minimal effective ranitidine doses of 300 mg for a decrease in mean H+, and 1200 mg for % time pH > or = 4.
  
  
  CONCLUSIONS
  If these higher doses of ranitidine are confirmed to be more effective than the standard 150 mg b.d. regimen for the treatment of patients with gastro-oesophageal reflux disease, then the mechanism of this action probably relates to the lower exposure of the oesophageal mucosa to acid.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: A B
authors.initials: AB
authors.lastname: Thomson
authors.forename: L
authors.initials: L
authors.lastname: Babiuk
authors.forename: P
authors.initials: P
authors.lastname: Kirdeikis
authors.forename: L
authors.initials: L
authors.lastname: Zuk
authors.forename: B
authors.initials: B
authors.lastname: Marriage
authors.forename: K
authors.initials: K
authors.lastname: Bowes
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004947:Esophagus / Q000187:drug effects; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D011187:Posture; D011899:Ranitidine / Q000008:administration & dosage / Q000627:therapeutic use*; D013270:Stomach / Q000187:drug effects
chemical_list: D011899:Ranitidine