Access the full text.
Sign up today, get DeepDyve free for 14 days.
(1995)
The biochemical basis of NSAID - induced damage to the gastrointestinal tract : A review and a hypothesis
I. Bjarnason, P. Smethurst, C. Fenn, Carole Lee, I. Menzies, A. Levi (1989)
Misoprostol reduces indomethacin-induced changes in human small intestinal permeabilityDigestive Diseases and Sciences, 34
K. Swingle, G. Moore, T. Grant (1976)
4-nitro-2-phenoxymethanesulfonanilide (R-805): a chemically novel anti-inflammatory agent.Archives internationales de pharmacodynamie et de therapie, 221 1
S. Somasundaram, H. Hayllar, S. Rafi, J. Wrigglesworth, A. Macpherson, I. Bjarnason (1995)
The biochemical basis of non-steroidal anti-inflammatory drug-induced damage to the gastrointestinal tract: a review and a hypothesis.Scandinavian journal of gastroenterology, 30 4
(1998)
A comparison of indomethacin and nimesulide , a selective cyclooxygenase - 2 inhibitor , on key pathophysiological steps in the pathogenesis of NSAID enteropathy in the rat
G. Sigthórsson, M. Jacob, J. Wrigglesworth, S. Somasundaram, I. Tavares, R. Foster, A. Røseth, S. Rafi, T. Mahmud, R. Simpson, I. Bjarnason (1998)
Comparison of indomethacin and nimesulide, a selective cyclooxygenase-2 inhibitor, on key pathophysiologic steps in the pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in the rat.Scandinavian journal of gastroenterology, 33 7
O. Tofanetti, I. Casciarri, P. V. Cipolla (1989)
Effect of nimesulide on cyclo-oxygenase activity in rat gastric mucosa and inflammatory exudateMed. Sci. Res., 17
T. Mahmud, Sue Rafi, D. Scott, John Wrigglesworth, Ingvar Bjarnason (1996)
Nonsteroidal antiinflammatory drugs and uncoupling of mitochondrial oxidative phosphorylation.Arthritis and rheumatism, 39 12
R. Langenbach, S. Morham, H. Tiano, C. Loftin, B. Ghanayem, P. Chulada, J. Mahler, Christopher Lee, E. Goulding, K. Kluckman, Hyung-Suk Kim, O. Smithies (1995)
Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulcerationCell, 83
I. Bjarnason, J. Hayllar, A. Macpherson, A. Russell (1993)
Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans.Gastroenterology, 104 6
(1999)
Faecal calprotectin: A simple method
S. Somasundaram, S. Rafi, J. Hayllar, G. Sigthórsson, M. Jacob, A. Price, A. Macpherson, T. Mahmod, D. Scott, J. Wrigglesworth, I. Bjarnason (1997)
Mitochondrial damage: a possible mechanism of the “topical” phase of NSAID induced injury to the rat intestineGut, 41
I. Bjarnason, A. Macpherson, D. Hollander (1995)
Intestinal permeability: an overview.Gastroenterology, 108 5
J. Tibble, R. Foster, G. Sigthórsson, D. Scott, A. Røseth, I. Bjarnason (1998)
Faecal calprotectin: A simple method for the diagnosis of NSAID-induced enteropathyGastroenterology, 114
(1991)
The anti-inflammatory, analgesic and antipyretic activity of nimesulide
A. Anthony, A. Dhillon, C. Thrasivoulou, R. Pounder, A. Wakefield (1995)
Pre‐ulcerative villous contraction and microvascular induced by indomethacin in the rat jejunum: a detailed morphological studyAlimentary Pharmacology & Therapeutics, 9
(1995)
Pre-ulcerative villous contraction
J. Tibble, G. Sigthórsson, R. Foster, D. Scott, M. Fagerhol, A. Røseth, I. Bjarnason (1999)
High prevalence of NSAID enteropathy as shown by a simple faecal testGut, 45
J. Svensson, K. Samuelsson (1983)
Inhibition of platelet function by low dose acetylsalicylic acid in patients with cerebrovascular disease.Thrombosis research, 31 3
L. Aabakken, S. Larsen, M. Osnes (1990)
Visual analogue scales for endoscopic evaluation of nonsteroidal anti-inflammatory drug-induced mucosal damage in the stomach and duodenum.Scandinavian journal of gastroenterology, 25 5
(1995)
Intestinal permeability: An overview, Gastroenterology108, 1566–1581
G. Sigthórsson, J. Tibble, J. Hayllar, I. Menzies, A. Macpherson, R. Moots, D. Scott, M. Gumpel, Ingvar Bjarnason (1998)
Intestinal permeability and inflammation in patients on NSAIDsGut, 43
G. Velo (1991)
The Anti-Inflammatory, Analgesic and Antipyretic Activity of Nimesulide in Experimental ModelsDrug Investigation, 3
A. Anthony, C. Trasivoulou, A. P. Dhillon (1995)
Pre-ulcerative villous contraction and microvascular occlusion induced by indomethacin in the rat jejunumAliment. Pharmacol. Ther., 9
G. Nygård, A. Anthony, C. Piasecki, M. Trevethick, M. Hudson, A. Dhillon, R. Pounder, A. Wakefield (1994)
Acute indomethacin-induced jejunal injury in the rat: early morphological and biochemical changes.Gastroenterology, 106 3
These studies assessed the gastrointestinal tolerability and cyclooxygenase (COX) selectivity of nimesulide in animals and man. Nimesulide (15 and 30 mg/kg) had no significant 'topical' toxicity in animals as assessed by in vivo mitochondrial morphologcal studies and no increase in small intestinal permeability or inflammation in rats. Similarly, these doses did not affect mucosal prostaglandins significantly and there were no ulcers. At the very high does of 60 mg/kg, nimesulide had some 'topical' toxicity and lost some of its COX-2 selectivity, but this was not associated with inflammation or ulcers. Indomethacin (10 mg/kg, equivalent to 15 mg/kg of nimesulide) altered all of the above parameters and led to small bowel ulcers. This suggests that the gastrointestinal tolerability of nimesulide is not only due to its COX-2 selectivity, but that it is also due to its lack of 'topical' toxicity. Thirty six healthy subjects participated in a randomised, double-blind, double-dummy crossover study (14 day treatment with a washout) of the effect of nimesulide (100 mg bid) and naproxen (500 mg bid) on the gastroduodenal mucosa and small intestine (absorption-permeability and inflammation). An assessment was also made on their COX selectivity. Nimesulide caused significantly less gastric (p = 0.0001) and duodenal (p = 0.0086) damage than naproxen. Naproxen increased intestinal permeability significantly (p = 0.004) and caused intestinal inflammation while nimesulide (p > 0.40) did not. Nimesulide had no significant (p > 0.1) effect on COX-1 dependant platelet aggregation, reduced serum thromboxane B2 levels moderately by 24-34% (p < 0.005) and decreased prostanoid generation in gastric biopsies by 9-30% (p > 0.5). By comparison, naproxen had significantly (p < 0.0001) greater effects on these functions: abolished platelet aggregation to arachidonic acid, suppressed serum thromboxane B2 levels by 98% and gastric prostaglandin production by 76-82%. Nimesulide inhibited lipopolysaccharide-induced PGE2 formation in whole blood to a significantly (p < 0.01) greater extent than naproxen. ___TAGSTART___BR___TAGEND___This study shows that nimesulide has a preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses. This selectivity is associated with minimal gastrointestinal damage in the short term.
Inflammopharmacology – Springer Journals
Published: Dec 21, 2004
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.