Gastroduodenal tolerability of highly specific cyclo-oxygenase-2 inhibitor.
Inhibition of constitutively expressed cyclo-oxygenase (COX-1) by NSAIDs is thought to play an important role is the gastrointestinal toxicity of NSAIDs. To minimise the intestinal toxicity of NSAIDS, highly selective COX-2 (induced at inflammatory sites) inhibitors have been developed. One such is flosulide. We assessed the gastroduodenal tolerability of flosulide (20 mg twice a day) in man and compared it with that of naproxen (500 mg twice a day) in a randomised, double blind crossover fashion in 19 patients with osteoarthrosis. Treatment period was 2 weeks with a 2-week washout period with endoscopy before and after each treatment. Gastroduodenal damage was assessed as by Lanza (Grades 0-4) and by the Gastroscopic Rating Scale (Grades 0-9). Flosulide was significantly better tolerated (p < 0.005, analyses of deviance) than naproxen. No stomach damage was seen in 13 (68%) patients following flosulide and 5 (37%) following naproxen (p < 0.001). Lanza scores following flosulide (0.58) were significantly better than that of naproxen (1.47) (p < 0.001). The duodenal damage was mild with both treatments. The selective COX-2 inhibitor, flosulide, is significantly better tolerated and causes less gastric mucosal damage than naproxen when given for two weeks.
Hayllar
J
J
Department of Medicine, Mt Isa Base Hospital, Queensland, Australia.
Bjarnason
I
I
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; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D007527:Isoenzymes; D007719:Knee Joint; D008297:Male; D008565:Membrane Proteins; D009288:Naproxen / Q000009:adverse effects / Q000627:therapeutic use*; D010003:Osteoarthritis / Q000188:drug therapy*; D015207:Osteoarthritis, Hip / Q000188:drug therapy*; D010544:Peroxidases / Q000037:antagonists & inhibitors*; D011451:Prostaglandin-Endoperoxide Synthases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007189:Indans; D007527:Isoenzymes; D008565:Membrane Proteins; D009288:Naproxen; D010544:Peroxidases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C059178:flosulide