A randomized, double-blind, single-center, crossover study was conducted to determine the effects of three different ranitidine regimens, including 150 mg b.d., 300 mg b.d., and 300 mg q.d.s., and placebo on intra-esophageal and intragastric pH in patients with gastro-esophageal reflux disease (GERD).

Twenty six symptomatic subjects with GERD were evaluated. A total of 9 subjects were included in the study who were treated with each of the regimens for 72 hrs, with a washout period of a minimum 48h after each dosing period. Normal meals and beverages were provided to all the participants.

The primary efficacy parameters examined included mean intragastric hydrogen ion activity (H+), median intragastric H+, and the percentage of time intra-esophageal pH was <4. Secondary efficacy parameters included median intragastric pH, total number of reflux episodes with an intra-esophageal pH of <4, and number of intra-esophageal reflux episodes which lasted more than 5 mins.

Findings of the study:

• 9% of the subjects completed the study (7 of 26).
• All three doses of ranitidine were effective.
• With increasing doses of ranitidine, a decrease was observed in the 24-h intragastric mean H+ and integrated H+; the percentage of time the pH was > 4 (% time pH > 4) increased.
• 300 mg daily was the minimal effective dose for these effects.
• With increasing doses of ranitidine, a progressive decline was noted in mean 24-h intra-esophageal H+ and integrated H+, and increase in % time pH >
• The minimal effective dose for intra-esophageal mean H+ and integrated H+ was 300 mg daily, and it was 600 mg for % time pH >
• 1200 mg was the minimal effective dose to decrease the number of reflex episodes.

The study concluded that if these higher doses of ranitidine were confirmed to be more effective than the standard 150 mg b.d. regimen for the treatment of GERD, then the mechanism of this action is possibly associated with decreased acid exposure of the esophagus.

Source:Thomson AB, Babiuk L, Kirdeikis P, et al. A dose-ranging study of ranitidine and its effect on intragastric and intra-oesophageal acidity in subjects with gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 1994;8(4):443-51.