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.
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).
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.
These results endorse the idea that highly selective Cox-2 inhibitors may be associated with lesser gastrointestinal side effects than conventional NSAIDs.