Abstract | 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. CONCLUSION: These results endorse the idea that highly selective Cox-2 inhibitors may be associated with lesser gastrointestinal side effects than conventional NSAIDs.
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Authors | I Bjarnason, A Macpherson, H Rotman, J Schupp, J Hayllar |
Journal | Scandinavian journal of gastroenterology
(Scand J Gastroenterol)
Vol. 32
Issue 2
Pg. 126-30
(Feb 1997)
ISSN: 0036-5521 [Print] England |
PMID | 9051872
(Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Cyclooxygenase 2 Inhibitors
- Cyclooxygenase Inhibitors
- Indans
- Isoenzymes
- Membrane Proteins
- Naproxen
- Cyclooxygenase 2
- PTGS2 protein, human
- Prostaglandin-Endoperoxide Synthases
- flosulide
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Topics |
- Adult
- Aged
- Anti-Inflammatory Agents, Non-Steroidal
(adverse effects, therapeutic use)
- Cross-Over Studies
- Cyclooxygenase 2
- Cyclooxygenase 2 Inhibitors
- Cyclooxygenase Inhibitors
(adverse effects, therapeutic use)
- Double-Blind Method
- Duodenum
(drug effects)
- Endoscopy, Gastrointestinal
- Female
- Gastrointestinal Diseases
(chemically induced, pathology)
- Humans
- Indans
(adverse effects, therapeutic use)
- Intestinal Mucosa
(drug effects)
- Isoenzymes
- Male
- Membrane Proteins
- Middle Aged
- Naproxen
(adverse effects, therapeutic use)
- Osteoarthritis
(drug therapy)
- Prostaglandin-Endoperoxide Synthases
- Stomach
(drug effects)
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