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.