Co-administration of naproxen or celecoxib with omeprazole and/or low-dose aspirin results in marked exacerbation of small intestinal damage.

<p>In contrast, rats given a naproxen derivative (ATB-346 or NCX 429) did not develop significant intestinal injury when given alone or in combination with omeprazole, low-dose aspirin, or both. *p<0.05, **p<0.01 versus the corresponding group treated with NSAID alone (n≥6 per group). Aspirin and omeprazole, alone or given together, did not elicit significant intestinal damage.</p

Effects of NSAIDs in rats with adjuvant arthritis.

<p>Despite comparable suppression of paw swelling (panel A), gastric prostaglandin synthesis (panel B) and whole blood thromboxane synthesis (panel C), ATB-346 and NCX 429 did not cause significant gastric (panel D) or intestinal (panel E) damage. Celecoxib also did not cause significant GI damage. *p<0.05, **p<0.01 versus the naproxen-treated group. n = 8 per group.</p

Increased naproxen-induced small intestinal damage in obese versus lean rats.

<p>Neither lean nor obese rats developed intestinal damage when given ATB-346. **p<0.01 versus the corresponding vehicle- and ATB-346-treated rats. n = 6 rats per group.</p

Serum and biliary levels of naproxen are significantly reduced in rats given a naproxen derivative (ATB-346 or NCX 429) as compared to the levels observed in rats given an equimolar dose of naproxen itself.

<p>The test drugs were administered twice-daily for 2 days. *p<0.05, **p<0001 versus the naproxen-treated group. n = 4 per group.</p

Older (19 months of age) rats develop extensive gastric damage when given naproxen, but not when given equimolar doses of a hydrogen sulfide-releasing naproxen derivative (ATB-346) or a nitric oxide-releasing naproxen derivative (NCX 429).

<p>***p<0.001 versus the vehicle-treated group. n =  6 rats per group.</p