The effects of indomethacin on gastroduodenal morphology and mucosal pH gradient in the healthy human stomach.

To define further the injury and the mechanisms of mucosal injury induced by indomethacin, the effect of 28-day continuous administration of oral indomethacin on gastroduodenal morphology, gastric histology, and the protective mucus-bicarbonate barrier overlying gastroduodenal mucosa in humans was studied. In the studies, indomethacin caused acute gastroduodenal damage in 100% of cases, with maximal damage at 24 hours of administration. With continued intake this damage resolves, although a minority (two study subjects) progressed to discrete ulceration. Why these two subjects failed to adapt is unknown. Biopsy specimens taken during the studies showed no significant changes in inflammatory or regenerative features, and thus failed to shed any light on this process of adaptation to damage. Mucosal pH gradient studies showed a significant increase in juxtamucosal pH at the time of maximal damage (24 hours); this is thought to represent passive diffusion of alkali from damaged mucosa. In conclusion, mucosal adaptation to acute damage by indomethacin occurs in humans. The mechanisms through which the mucosa adapts in this intriguing way remain unknown.