A randomized, double-blind, crossover comparative endoscopy study on the gastroduodenal tolerability of a highly specific cyclooxygenase-2 inhibitor, flosulide, and naproxen.
BACKGROUND
Inhibition of constitutively expressed cyclooxygenase (Cox-1) is thought to play an important role in the gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs (NSAID), while their therapeutic action may be due to inhibition of the enzyme Cox-2, which is specifically expressed at sites of inflammation. NSAIDs with high affinity and specifity for Cox-2 hold the promise of maintaining efficacy without the gastrointestinal side effects of conventional NSAIDs.


METHODS
We assessed the gastrointestinal tolerability of flosulide (20 mg twice a day), a highly selective Cox-2 inhibitor with that of naproxen (500 mg twice a day), which has equal affinity for Cox-1 and -2 in 19 patients with osteoarthrosis in a randomized, double blind, crossover endoscopy study. Subjects were treated for 2 weeks with a 2-week washout period. Gastroduodenal damage was primarily assessed as by Lanza (grades 0-4).


RESULTS
No stomach damage was seen in 13 (68%) patients after flosulide and in 5 (37%) after naproxen (P < 0.001). Lanza scores were significantly lower after flosulide (0.58) than after naproxen (1.47) (P < 0.001; odds ratio, 84.4; 95% confidence interval, 1.45-4908). Flosulide was significantly better tolerated (P < 0.005) than naproxen.


CONCLUSIONS
These results endorse the idea that highly selective Cox-2 inhibitors may be associated with lesser gastrointestinal side effects than conventional NSAIDs.
Bjarnason
I
I
Dept. of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, UK.
Macpherson
A
A
Rotman
H
H
Schupp
J
J
Hayllar
J
J
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004386:Duodenum / Q000187:drug effects; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D007189:Indans / Q000009:adverse effects* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000187:drug effects; D007527:Isoenzymes; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009288:Naproxen / Q000009:adverse effects* / Q000627:therapeutic use; D010003:Osteoarthritis / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases; D013270:Stomach / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007189:Indans; D007527:Isoenzymes; D008565:Membrane Proteins; D009288:Naproxen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C059178:flosulide