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Gastroenterology. 1994 Jul;107(1):173-9.

Novel nonsteroidal anti-inflammatory drug derivatives with markedly reduced ulcerogenic properties in the rat.

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  • 1Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.



The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is limited by their ability to induce gastrointestinal injury. Two NSAIDs were modified by incorporation of an nitroxybutyl moiety. The short-term ulcerogenic and anti-inflammatory properties of these derivatives were compared with the native NSAIDs.


Rats were given flurbiprofen, ketoprofen, or their respective derivatives, and the extent of gastric damage and effect on gastric prostaglandin E2 synthesis was assessed. The damage-promoting effects of these compounds were also compared following twice-daily administration for 1 week. Anti-inflammatory properties were examined using a carrageenan-induced paw edema model.


The derivatives of flurbiprofen and ketoprofen caused significantly less short-term gastric mucosal injury at all doses tested, despite producing comparable suppression of prostaglandin synthesis. The NSAID derivatives also showed comparable anti-inflammatory activity to the native compounds. The flurbiprofen derivative inhibited collagen-induced platelet aggregation significantly more than the native NSAID. Plasma nitrate/nitrite levels increased significantly following administration of the flurbiprofen derivative, consistent with release of a nitrogen oxide.


Addition of a nitroxybutyl moiety to two NSAIDs markedly reduced the ability of these agents to induce short-term gastric injury but did not interfere with their ability to suppress inflammatory processes, inhibit prostaglandin synthesis, or inhibit platelet aggregation. These NSAID derivatives may therefore represent a novel class of anti-inflammatory drugs with markedly less ulcerogenic effects on the stomach.

[PubMed - indexed for MEDLINE]
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