Effect of Increasing Doses of Ranitidine on Exposure of the Oesophagus to Gastric Acid in Patients with Reflux Oesophagitis

Abstract

To investigate the effect of doses of ranitidine higher than those presently recommended for the treatment of patients with reflux oesophagitis on features of gastro-oesophageal reflux, we compared the effect of two times 300 mg and four times 300 mg ranitidine daily on gastro-oesophageal reflux features measured by continuous 24-h ambulatory pH-metry, 5 cm above the manometrically determined lower oesophageal sphincter in eight patients with erosive or ulcerative reflux oesophagitis resistant to ranitidine treatment with twice daily 150 mg for 12 weeks. During both higher doses of ranitidine there were significant decreases in the total number of reflux episodes with a pH below 4.0 (p < 0.05 and p <0.01, respectively), the number of episodes with pH below 4.0 lasting longer than 5 min (p < 0.01), and the fraction of time that the oesophagus was exposed to reflux with pH < 4.0 (p <0.01) when compared with no treatment. The median pH in the oesophagus was significantly increased by the two doses of ranitidine (p <0.05). Four times 300 mg of ranitidine daily was more effective than twice daily 300 mg in reducing the total number of reflux episodes with pH < 4.0 and the fraction of time that the intra-oesophageal pH was below 4.0 (p <0.05). Because clinical studies have demonstrated that gastric acid in the refluent is the major factor responsible for the development of reflux oesophagitis, these data pave the way for clinical studies of the effect of higher doses of ranitidine than presently used in the treatment of patients with reflux oesophagitis.

Key Words:

• Dose finding
• histamine H₂-receptor antagonist
• pH
• ranitidine
• reflux oesophagitis