The effects of esomeprazole combined with aspirin or rofecoxib on prostaglandin E2 production in patients with Barrett's oesophagus.
BACKGROUND
Reducing mucosal cyclo-oxygenase-2 and prostaglandin E(2) production and suppressing intraoesophageal acid may be effective chemopreventive strategies in patients with Barrett's oesophagus.


OBJECTIVE
To compare the effects of aspirin and rofecoxib when administered with esomeprazole on prostaglandin E(2) production, cyclo-oxygenase-2 expression and proliferating cell nuclear antigen expression in patients with Barrett's oesophagus.


METHODS
This exploratory, multicentre, randomized, open-label, four-way crossover study in 45 patients with Barrett's oesophagus evaluated prostaglandin E(2) content, proliferating cell nuclear antigen expression, and cyclo-oxygenase-2 expression after 10 days of sequential treatments with: esomeprazole 40 mg twice daily plus aspirin 325 mg once daily (E40 b.d. + A325); E40 b.d. plus rofecoxib 25 mg once daily (E40 b.d. + R25); E40 b.d.; and rofecoxib 25 mg once daily (R25).


RESULTS
Prostaglandin E(2) content reduction in Barrett's oesophagus tissue was significantly greater with E40 b.d. + A325 compared with E40 b.d. + R25, E40 b.d. or R25 (P < 0.05). All treatments containing E40 b.d. significantly decreased proliferating cell nuclear antigen expression from baseline (P < 0.05). None of the treatments significantly reduced cyclo-oxygenase-2 expression.


CONCLUSIONS
The combined treatment of esomeprazole 40 mg b.d. and aspirin 325 mg significantly decreased mucosal prostaglandin E(2) content and all treatments containing esomeprazole significantly reduced proliferating cell nuclear antigen expression in patients with Barrett's oesophagus.
Stanford University School of Medicine, CA 94305, USA. vagt@stanford.edu
G
G
Triadafilopoulos
B
B
Kaur
S
S
Sood
B
B
Traxler
D
D
Levine
A
A
Weston
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2 / Q000032:analysis; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015232:Dinoprostone / Q000032:analysis*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D064098:Esomeprazole / Q000009:adverse effects / Q000627:therapeutic use*; D004941:Esophagitis / Q000150:complications / Q000378:metabolism; D004947:Esophagus / Q000737:chemistry; D005260:Female; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011446:Prospective Studies; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007783:Lactones; D018809:Proliferating Cell Nuclear Antigen; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D064098:Esomeprazole; D001241:Aspirin