Rofecoxib, a COX-2 inhibitor, does not inhibit human gastric mucosal prostaglandin production

Background & Aims: Rofecoxib, an inhibitor of the inducible cyclooxygenase (COX)-2 enzyme, appears not to cause acute gastroduodenal injury or chronic ulceration, To attribute this to COX-2 selectivity with sparing of gastric mucosal prostaglandin synthesis requires direct proof. Methods: Twenty-fou r healthy, nonsmoking Helicobacter pylori-negative volunteers were randomiz ed to 1 of 2 separate concurrent blinded crossover studies. Sixteen volunte ers received rofecoxib, 50 mg once daily, for 5 days in one treatment perio d and placebo in the other. Eight volunteers similarly received naproxen, 5 00 mg twice daily, and placebo. On day 5 of each period, antral mucosal pro staglandin E-2 (PGE(2)) synthesis was measured by radioimmunoassay after vo rtexing for 3 minutes. Whole blood COX-1 activity was measured as serum thr omboxane (TXB)(2)- and COX-2 activity as lipopolysaccharide (LPS)-induced P GE(2), Results: Naproxen decreased gastric mucosal FGE(2) synthesis by 65% (90% confidence interval [CI], 53%-74%; P = 0.001 vs. placebo) in contrast to an 18% increase after rofecoxib (90% CI, -11% to 57%; P = 0.313 vs. plac ebo). Naproxen also significantly inhibited both serum TXB, by 94% and LPS- induced PGE(2) production by 77% (both P less than or equal to 0.002 vs. pl acebo), but rofecoxib only inhibited COX-2-dependent LPS-induced PGE(2) (by 79%; P < 0.001 vs. placebo). Conclusions: Rofecoxib (50 mg) lacked naproxe n's ability to reduce the availability of gastroprotective prostaglandins.