Rofecoxib, a COX-2 inhibitor, does not inhibit human gastric mucosal prostaglandin production.
OBJECTIVE
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-four healthy, nonsmoking Helicobacter pylori-negative 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 COX-1 activity was measured as serum thromboxane (TXB)2- and COX-2 activity as lipopolysaccharide (LPS)-induced PGE2.


RESULTS
Naproxen decreased gastric mucosal PGE2 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. placebo). Naproxen also significantly inhibited both serum TXB2 by 94% and LPS-induced PGE2 production by 77% (both P < or = 0.002 vs. placebo), but rofecoxib only inhibited COX-2-dependent LPS-induced PGE(2) (by 79%; P < 0.001 vs. placebo).


CONCLUSIONS
Rofecoxib (50 mg) lacked naproxen's ability to reduce the availability of gastroprotective prostaglandins.
Wight
N J
NJ
Division of Gastroenterology, University Hospital, Nottingham, England.
Gottesdiener
K
K
Garlick
N M
NM
Atherton
C T
CT
Novak
S
S
Gertz
B J
BJ
Calder
N A
NA
Cote
J
J
Wong
P
P
Dallob
A
A
Hawkey
C J
CJ
D000328:Adult; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000097:blood; D007783:Lactones / Q000009:adverse effects / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D009288:Naproxen / Q000009:adverse effects / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D011453:Prostaglandins / Q000096:biosynthesis*; D013450:Sulfones; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000097:blood
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011453:Prostaglandins; D013450:Sulfones; C116926:rofecoxib; D013929:Thromboxane B2; D009288:Naproxen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases