Etodolac, a racemic nonsteroidal anti‐inflammatory drug, exhibits low gastrointestinal toxicity: relation to the effects of the enantiomers (840.13)

Abstract

Etodolac, a racemic (LR) nonsteroidal anti‐inflammatory drug (NSAID), has higher gastric safety compared to other conventional NSAIDs. However, it remains unknown whether the LR etodolac shows less adverse action in the small intestine. In the present study, we examined the effect of etodolac, both L/R and the enantiomers (S and R) on the gastric and small intestinal mucosa. Methods: Male SD rats were used. Etodolac (5‐50 mg/kg), both LR, S and R, was given p.o. in 18 h‐fasted or non‐fasted rats, and the stomach or the small intestine was examined for lesions 4 or 24 h later, respectively. Results: LR‐etodolac and S‐etodolac dose‐dependently caused lesions in both the stomach and small intestine, yet the effect of the former was much less potent compared to the latter. R‐etodolac did not cause damage even at 50 mg/kg. On the other hand, pretreatment with R‐etodolac dose‐dependently prevented the development of gastric lesions induced by indomethacin. The mucosal PGE2 content in the stomach and small intestine was significantly decreased by both LR‐etodolac and S‐etodolac, but not R‐etodolac. Conclusion: These results suggest that LR‐etodolac has less ulcerogenic properties in the gastrointestinal mucosa and showed that this safety profile of LR‐etodolac may be explained by the mucosal protective action of R‐etodolac.