Pharmacology and gastrointestinal safety of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor: an integrated study

Atherton, Clare T.; Jones, John I.; McKaig, Brian; Bebb, James R.; Cunliffe, Rob; Burdsall, Jake; Brough, Joanne L.; Stevenson, Diane; Bonner, Johanne; Rordorf, Christiane; Scott, Graham; Branson, Janice; Hawkey, Christopher J.

doi:10.1016/s1542-3565(03)00318-5

Cited by 41 publications

(46 citation statements)

References 29 publications

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“…Nimesulide, 71 celecoxib, 62 rofecoxib, 75 and lumiracoxib 74 do not increase small intestinal permeability when taken short term.…”

Section: Cox-2 Selective Agentsmentioning

confidence: 93%

“…73 Lumiracoxib, which is classifi ed as a COX-2 selective agent (coxib), despite resembling diclofenac and inhibiting gastric COX-1 signifi cantly is purported not to increase intestinal permeability even though it has a low pKa. 74 What is of interest is that these short-term permeability studies can be translated to long-term usage in most cases. Hence the same drugs that increase intestinal permeability in the short term are also associated with increased permeability when given long term.…”

Section: Small Intestinal Permeability In Humansmentioning

confidence: 99%

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Intestinal permeability in the pathogenesis of NSAID-induced enteropathy

Bjarnason

Takeuchi²

2009

J Gastroenterol

136

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NSAID enteropathy is associated with significant morbidity and occasionally mortality. There are no proven effective ways of preventing this damage. Because increased intestinal permeability appears to be a central mechanism in the pathogenesis of NSAID enteropathy, it becomes a potential therapeutic target for prevention. At present there are a number of ways to limit the increased permeability, but additional studies are required to assess if this approach reduces the prevalence and severity of NSAID enteropathy.

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“…Nimesulide, 71 celecoxib, 62 rofecoxib, 75 and lumiracoxib 74 do not increase small intestinal permeability when taken short term.…”

Section: Cox-2 Selective Agentsmentioning

confidence: 93%

Section: Small Intestinal Permeability In Humansmentioning

confidence: 99%

Intestinal permeability in the pathogenesis of NSAID-induced enteropathy

Bjarnason

Takeuchi²

2009

J Gastroenterol

136

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“…The lack of intestinal damage with this class of drugs in animal experiments [24, 39, 40] has been confirmed in clinical studies [23,41,42,43]. Most patients taking either meloxicam [27] or nimesulide [44], two preferential COX-2 inhibitors, had normal intestinal permeability and no increase in intestinal inflammation in comparison to control patients not taking the drug.…”

Section: Lesions Induced By Nsaids In the Distal Gi Tractmentioning

confidence: 94%

Microbial Flora in NSAID-Induced Intestinal Damage: A Role for Antibiotics?

Lanas

Scarpignato

2006

Digestion

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Upper gastrointestinal (GI) complications are well-recognized adverse events associated with non-steroidal anti-inflammatory drug (NSAID) use. However, NSAID-induced damage to the distal GI tract is also common and more frequent than previously recognized. These untoward effects include increased mucosal permeability, mucosal inflammation, anemia and occult blood loss, malabsorption, protein loss, ileal dysfunction, diarrhea, mucosal ulceration, strictures due to diaphragm disease as well as active bleeding and perforation. Studies with selective COX-2 inhibitors have shown that, in the short term, these agents do not increase mucosal permeability and display a reduced by 50% incidence of serious lower GI side effects compared to traditional NSAIDs. However, the long-term use of this therapeutic strategy is limited by the increased risk of serious cardiovascular events, especially in patients with multiple risk factors. Several studies have suggested that intraluminal bacteria play a significant role in the pathogenesis of small-bowel damage induced by NSAIDs and that enterobacterial translocation into the mucosa represents the first step that sets in motion a series of events leading to gross lesion formation. Experimental and clinical investigations indicate that in the short term, antibacterial agents either reduce or abolish NSAID enteropathy. However, potential adverse effects of systemic antimicrobials and the possible occurrence of drug resistance have so far precluded this interesting approach. The availability of poorly absorbed and effective antibiotics, like rifaximin, may represent an attractive alternative to prevent or limit NSAID-associated intestinal damage.

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“…18 Endoscopic studies in volunteers and patients have shown a reduced effect on acute GI injury, prostaglandin synthesis and medium-term development of ulcers compared with ibuprofen 19,20 and naproxen. 21,22 We set up the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) in order to evaluate directly whether lumiracoxib would reduce the incidence of ulcer complications over 52 weeks in patients with OA. Whilst this is now a necessary part of the evaluation for registration of any COX-2 selective inhibitor in the USA, it is of particular interest for lumiracoxib, given its structurally distinct nature.…”

mentioning

confidence: 99%

Therapeutic Arthritis Research and Gastrointestinal Event Trial of lumiracoxib – study design and patient demographics

Hawkey

Farkouh

Gitton

et al. 2004

Aliment Pharmacol Ther

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SUMMARYBackground: Cyclooxygenase-2 selective inhibitors were developed in order to reduce the incidence of life-threatening gastrointestinal ulcer complications compared with non-selective non-steroidal anti-inflammatory drugs. Previous outcomes studies have, variously, lacked power to investigate this endpoint, focused on broader outcomes, or been too small to quantify the influence of aspirin. Aim: To evaluate lumiracoxib, a novel cyclooxygenase-2 selective inhibitor, vs. non-selective non-steroidal anti-inflammatory drugs in an outcomes study of considerably increased size. This paper describes the study's methodology. Methods and patients: The Therapeutic Arthritis Research and Gastrointestinal Event Trial was a rand-

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Pharmacology and gastrointestinal safety of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor: an integrated study

Cited by 41 publications

References 29 publications

Intestinal permeability in the pathogenesis of NSAID-induced enteropathy

Intestinal permeability in the pathogenesis of NSAID-induced enteropathy

Microbial Flora in NSAID-Induced Intestinal Damage: A Role for Antibiotics?

Therapeutic Arthritis Research and Gastrointestinal Event Trial of lumiracoxib – study design and patient demographics

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