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BACKGROUND: Tolerance has been shown to develop in duodenal ulcer patients receiving H2-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 14C 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 decrease 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 seen to contribute to increased gastro-oesophageal reflux in individual patients.
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Hatlebakk et al. (1996) studied this question.
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