Gastro-oesophageal reflux during 3 months of therapy with ranitidine in reflux oesophagitis

Background: Tolerance has been shown to develop in duodenal ulcer patients receiving H-2-receptor antagonists, particularly with increased doses. Development of tolerance to ranitidine and its possible consequences for oesophageal acid load in patients with gastro-oesophageal reflux disease has still to be established. Methods: Eighteen patients with reflux oesophagitis grade 1 were treated with 300 mg ranitidine twice daily for 3 months and examined with two-channel 23-h pH-metry in the distal oesophagus and gastric body at base line and after 3 days and 3 months. Gastric infection with Helicobacter pylori was assessed with the C-14 urea breath test. Results: Median 23-h gastric pH increased significantly from 1.5 at base line to 3.7 on day 3 and 2.8 after 3 months but decreased significantly from day 3 to month 3 of therapy. Median 23-h acid reflux time was reduced significantly by therapy, from 12.6% at base line to 6.2% on day 3 and 7.2% after 3 months, and there was no significant difference between day 3 and month 3. Although there was no significant change in commonly used indicators of gastro-oesophageal reflux, interindividual variation was great, and multiple linear regression analysis indicated that tolerance, expressed as change in median gastric pH, was related to individual changes in 23-h acid reflux time with a correlation coefficient of -0.43. Infection with H. pylori was diagnosed in 44% of patients and was negatively related to tolerance. Conclusions: Our group of patients developed tolerance to the effect of ranitidine on gastric acidity. While gastro-oesophageal reflux did not change significantly in the group, tolerance may seem to contribute to increased gastro-oesophageal reflux in individual patients.