We assessed the intraluminal pH and mucosal
prostaglandin E2 (
PGE2) concentrations in patients (nonresponders) whose
gastric ulcer did not heal after an initial 2 months and subsequent 3 months of treatment with one of five H2-receptor antagonists (H2RAs). The efficacy of
misoprostol, a
PGE1 analogue, or
AG-1749, a
proton-pump inhibitor, on
ulcer healing in nonresponders was also tested. The percentage of time (24-h measurement) during which the pH was 3 or more was higher in the basal condition (no H2RA) in nonresponders than in good responders with healing in the first 2 months. H2RAs increased this percentage satisfactorily in nonresponders as well as in good responders. The mean mucosal
PGE2 concentration in the
ulcer rim was 26 ng/g of tissue in nonresponders, much lower than in good responders. Treatment with
misoprostol combined with an H2RA resulted in 60% success for
ulcer healing within the next 2 months in nonresponders, without affecting the intraluminal pH measured during treatment with an H2RA alone.
AG-1749 raised the percentage of time with high pH to 99% from the 68% obtained with an H2RA and cured 88% of this type of
ulcer. These results suggest that extremely low
PGE2 levels in gastric mucosa are related to the effectiveness of the H2RA. In such a condition, the small amount of gastric acid that is still secreted even during treatment with an H2RA may interrupt
ulcer healing. Therefore, treatment with a
prostaglandin analogue combined with an H2RA or treatment with a
proton-pump inhibitor may be useful for
ulcer healing in nonresponders.