Complementary studies of the gastrointestinal safety of the cyclo‐oxygenase‐2‐selective inhibitor etoricoxib

Hunt, Richard H.; Harper, Sean E.; Callegari, Peter E.; Yu, Chang; Quan, Hui; Evans, Judith K.; James, Cindy; Bowen, Barry M.; Rashid, Ferid

doi:10.1046/j.1365-2036.2003.01407.x

Cited by 99 publications

(68 citation statements)

References 38 publications

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“…In addition, etoricoxib elicited both type 2 and 3 lesions, particularly in the ileum. However, these injuries were not associated with significant reductions of blood hemoglobin, an effect consistent with the lack of increase in fecal blood loss in humans (Hunt et al, 2003). With regard for the mechanisms underlying etoricoxib enteropathy, our data suggest a direct topic action.…”

Section: Discussionsupporting

confidence: 78%

NSAID-Induced Enteropathy: Are the Currently Available Selective COX-2 Inhibitors All the Same?

Fornai

Antonioli

Colucci

et al. 2013

J Pharmacol Exp Ther

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Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce intestinal mucosal damage, but the underlying mechanisms remain poorly understood. The present study investigated the effects of celecoxib, etoricoxib, indomethacin, and diclofenac on small bowel integrity in rats. Male rats were treated orally with test drugs for 14 days. Animals were processed for assessment of blood hemoglobin levels and hepatic mitochondrial functions, microscopic evaluation of small intestinal damage, Western blot analysis of cyclooxygenase-1 and -2 (COX-1, COX-2) expression, and assay of malondialdehyde (MDA), myeloperoxidase (MPO), and prostaglandin E 2 (PGE 2 ) levels in small intestine. Indomethacin and diclofenac decreased blood hemoglobin levels, whereas etoricoxib and celecoxib were without effects. Celecoxib caused a lower degree of intestinal damage in comparison with the other test drugs. Indomethacin and diclofenac, but not etoricoxib or celecoxib, reduced intestinal PGE 2 levels. Test drugs did not modify intestinal COX-1 expression, although they enhanced COX-2, with the exception of celecoxib, which downregulated COX-2. Indomethacin, diclofenac, and etoricoxib altered mitochondrial respiratory parameters, although celecoxib was without effects. Indomethacin or diclofenac increased MDA and MPO levels in both jejunum and ileum. In the jejunum, etoricoxib or celecoxib did not modify such parameters, whereas in the ileum, etoricoxib, but not celecoxib, increased both MDA and MPO levels. These findings suggest that nonselective NSAIDs and etoricoxib can induce enteropathy through a topic action, whereas celecoxib lacks relevant detrimental actions. The selectivity profile of COX-1/COX-2 inhibition by test drugs and the related effects on prostaglandin production do not appear to play a major role in the pathogenesis of enteropathy.

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Section: Discussionsupporting

confidence: 78%

NSAID-Induced Enteropathy: Are the Currently Available Selective COX-2 Inhibitors All the Same?

Fornai

Antonioli

Colucci

et al. 2013

J Pharmacol Exp Ther

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“…253,257 Both studies used etoricoxib 120 mg/day (supra-licensed dose), one included OA patients and another included both OA and RA patients. Cumulative incidences of ulcers were calculated using survival analysis methods, taking into account patient withdrawals.…”

Section: Endoscopic Gi Ulcersmentioning

confidence: 99%

Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation

Chen

Jobanputra²,

Barton³

et al. 2008

Health Technol Assess

271

174

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“…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. In studies performed in healthy volunteers, rofecoxib [41] and etoricoxib [45] – conversely from traditional NSAIDs (namely indomethacin or ibuprofen) – proved to be unable of increasing fecal blood loss. Along the same lines, the incidence of anemia with celecoxib was significantly lower than that seen with traditional NSAIDs [10, 46].…”

Section: Lesions Induced By Nsaids In the Distal Gi Tractmentioning

confidence: 99%

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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Complementary studies of the gastrointestinal safety of the cyclo‐oxygenase‐2‐selective inhibitor etoricoxib

Cited by 99 publications

References 38 publications

NSAID-Induced Enteropathy: Are the Currently Available Selective COX-2 Inhibitors All the Same?

NSAID-Induced Enteropathy: Are the Currently Available Selective COX-2 Inhibitors All the Same?

Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation

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

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