rofecoxib a cox2 inhibitor does not inhibit human gastric mucosal prostaglandin production background aims rofecoxib an inhibitor of the inducible cyclooxygenase cox2 enzyme appears not to cause acute gastroduodenal injury or chronic ulceration to attribute this to cox2 selectivity with sparing of gastric mucosal prostaglandin synthesis requires direct proofmethods twentyfour healthy nonsmoking helicobacter pylorinegative volunteers were randomized to 1 of 2 separate concurrent blinded crossover studies sixteen volunteers received rofecoxib 50 mg once daily for 5 days in one treatment period and placebo in the other eight volunteers similarly received naproxen 500 mg twice daily and placebo on day 5 of each period antral mucosal prostaglandin e2 pge2 synthesis was measured by radioimmunoassay after vortexing for 3 minutes whole blood cox1 activity was measured as serum thromboxane txb2 and cox2 activity as lipopolysaccharide lpsinduced pge2results naproxen decreased gastric mucosal pge2 synthesis by 65 90 confidence interval ci 5374 p 0001 vs placebo in contrast to an 18 increase after rofecoxib 90 ci 11 to 57 p 0313 vs placebo naproxen also significantly inhibited both serum txb2 by 94 and lpsinduced pge2 production by 77 both p or 0002 vs placebo but rofecoxib only inhibited cox2dependent lpsinduced pge2 by 79 p 0001 vs placeboconclusions rofecoxib 50 mg lacked naproxens ability to reduce the availability of gastroprotective prostaglandins