BACKGROUND: Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal anti-inflammatory drugs. AIMS: We compared the biochemical and gastrointestinal effects of nimesulide, a potent and selective COX-2 inhibitor, with naproxen which exhibits no selectivity. SUBJECTS:Thirty six healthy volunteers were randomised to nimesulide 100 mg or naproxen 500 mg twice daily for two weeks in a double blind, crossover study with a washout between treatments. METHODS:Gastrointestinal side effects were assessed by endoscopy, and by estimation of small intestinal absorption-permeability and inflammation. Comparisons were made between variables at the end of each treatment phase. RESULTS:Nimesulide caused significantly less gastric injury using the modified Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039). Nimesulide had lower visual analogue scores (VAS) for haemorrhage and erosive lesions in the stomach (p<0.001) and for mucosal injection in the duodenum (p=0.039). Naproxen increased excretion of calprotectin, a marker of intestinal inflammation (5.5 (1.2) to 12.1 (2.1) mg/l) while nimesulide had no effect (treatment difference p=0.03). Naproxen abolished platelet aggregation to arachidonic acid and suppressed serum thromboxane B(2) (TXB(2)) by 98%, indices of COX-1 activity. In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB(2) by 29%. Production of prostaglandin E(2) and prostacyclin by gastric biopsies, also COX-1 dependent, was inhibited by naproxen, but not by nimesulide. COX-2 activity, determined as endotoxin induced prostaglandin E(2) formation in plasma, was markedly suppressed by both treatments. INTERPRETATION:Nimesulide has preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses and induces less gastrointestinal damage than that seen with naproxen in the short term.
RCT Entities:
BACKGROUND: Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal anti-inflammatory drugs. AIMS: We compared the biochemical and gastrointestinal effects of nimesulide, a potent and selective COX-2 inhibitor, with naproxen which exhibits no selectivity. SUBJECTS: Thirty six healthy volunteers were randomised to nimesulide 100 mg or naproxen 500 mg twice daily for two weeks in a double blind, crossover study with a washout between treatments. METHODS: Gastrointestinal side effects were assessed by endoscopy, and by estimation of small intestinal absorption-permeability and inflammation. Comparisons were made between variables at the end of each treatment phase. RESULTS:Nimesulide caused significantly less gastric injury using the modified Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039). Nimesulide had lower visual analogue scores (VAS) for haemorrhage and erosive lesions in the stomach (p<0.001) and for mucosal injection in the duodenum (p=0.039). Naproxen increased excretion of calprotectin, a marker of intestinal inflammation (5.5 (1.2) to 12.1 (2.1) mg/l) while nimesulide had no effect (treatment difference p=0.03). Naproxen abolished platelet aggregation to arachidonic acid and suppressed serum thromboxane B(2) (TXB(2)) by 98%, indices of COX-1 activity. In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB(2) by 29%. Production of prostaglandin E(2) and prostacyclin by gastric biopsies, also COX-1 dependent, was inhibited by naproxen, but not by nimesulide. COX-2 activity, determined as endotoxin induced prostaglandin E(2) formation in plasma, was markedly suppressed by both treatments. INTERPRETATION:Nimesulide has preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses and induces less gastrointestinal damage than that seen with naproxen in the short term.
Authors: I K Khanna; R M Weier; Y Yu; P W Collins; J M Miyashiro; C M Koboldt; A W Veenhuizen; J L Currie; K Seibert; P C Isakson Journal: J Med Chem Date: 1997-05-23 Impact factor: 7.446
Authors: S Fu; K S Ramanujam; A Wong; G T Fantry; C B Drachenberg; S P James; S J Meltzer; K T Wilson Journal: Gastroenterology Date: 1999-06 Impact factor: 22.682
Authors: G Sigthorsson; M Jacob; J Wrigglesworth; S Somasundaram; I Tavares; R Foster; A Roseth; S Rafi; T Mahmud; R Simpson; I Bjarnason Journal: Scand J Gastroenterol Date: 1998-07 Impact factor: 2.423
Authors: G Sigthorsson; J Tibble; J Hayllar; I Menzies; A Macpherson; R Moots; D Scott; M J Gumpel; I Bjarnason Journal: Gut Date: 1998-10 Impact factor: 23.059
Authors: B F McAdam; F Catella-Lawson; I A Mardini; S Kapoor; J A Lawson; G A FitzGerald Journal: Proc Natl Acad Sci U S A Date: 1999-01-05 Impact factor: 11.205
Authors: C C Chan; S Boyce; C Brideau; A W Ford-Hutchinson; R Gordon; D Guay; R G Hill; C S Li; J Mancini; M Penneton Journal: J Pharmacol Exp Ther Date: 1995-09 Impact factor: 4.030