Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a randomized, open-label, controlled, multicenter, 12-week study, the efficacy and safety of nabumetone (1,000-2,000 mg/day) versus diclofenac (100-200 mg/day), naproxen (500-1,500 mg/day), ibuprofen (1,200-3,200 mg/day), or piroxicam (10-20 mg/day) were evaluated in patients with osteoarthritis (OA) or rheumatoid arthritis (RA). The results in elderly patients (> or = 65 years of age) are presented. Nabumetone was as effective as the comparator nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of elderly OA and RA patients. Ibuprofen and diclofenac caused significantly (p < 0.05) more abdominal pain than nabumetone (8.5%, 13.1%, and 4.1%, respectively). The frequency of abdominal pain was dose related for all NSAIDs except nabumetone. Diarrhea was reported by significantly (p < 0.02) more nabumetone-treated (6.6%) than ibuprofen-treated (0.9%) elderly patients, but the incidence of diarrhea was not dose related. There were no clinically significant changes in renal function with nabumetone or the comparator NSAIDs. A significant change in hepatic enzymes occurred in elderly patients treated with diclofenac (3.3%), which was different than for patients treated with nabumetone (p < 0.04), naproxen (p < 0.06), or ibuprofen (p < 0.06). With regard to withdrawals for adverse events, more (p < 0.04) piroxicam-treated patients (4.9%) withdrew than nabumetone-treated patients (1%). In addition, doubling the dose of nabumetone from 1,000 mg/day to 2,000 mg/day did not result in a proportional increase in adverse events. However, with the comparator NSAIDs, proportional increases in adverse events occurred with increased dose. Finally, the efficacy and safety of nabumetone in elderly patients were similar to the efficacy and safety observed in nonelderly patients.
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PMID:Efficacy and safety of nabumetone versus diclofenac, naproxen, ibuprofen, and piroxicam in the elderly. 835 98

Nabumetone is a nonsteroidal anti-inflammatory prodrug, which exerts its pharmacological effects via the metabolite 6-methoxy-2-naphthylacetic acid (6-MNA). Nabumetone itself is non-acidic and, following absorption, it undergoes extensive first-pass metabolism to form the main circulating active metabolite (6-MNA) which is a much more potent inhibitor of preferentially cyclo-oxygenase (COX)-2. The three major metabolic pathways of nabumetone are O-demethylation, reduction of the ketone to an alcohol, and an oxidative cleavage of the side-chain occurs to yield acetic acid derivatives. Essentially no unchanged nabumetone and < 1% of the major 6-MNA metabolite are excreted unchanged in the urine from which 80% of the dose can be recovered and another 10% in faeces. Nabumetone is clinically used mainly for the management of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) to reduce pain and inflammation. The clinical efficacy of nabumetone has also been evaluated in patients with ankylosing spondylitis, soft tissue injuries and juvenile RA. The optimum oral dosage of nabumetone for OA patients is 1 g once daily, which is well tolerated. The therapeutic response is superior to placebo and similar to nonselective COX inhibitors. In RA patients, nabumetone 1 g at bedtime is optimal, but an additional 0.5-1 g can be administered in the morning for patients with persistent symptoms. In RA, nabumetone has shown a comparable clinical efficacy to aspirin (acetylsalicylic acid), diclofenac, piroxicam, ibuprofen and naproxen. Clinical trials and a decade of worldwide safety data and long-term postmarketing surveillance studies show that nabumetone is generally well tolerated. The most frequent adverse effects are those commonly seen with COX inhibitors, which include diarrhoea, dyspepsia, headache, abdominal pain and nausea. In common with other COX inhibitors, nabumetone may increase the risk of GI perforations, ulcerations and bleedings (PUBs). However, several studies show a low incidence of PUBs, and on a par with the numbers reported from studies with COX-2 selective inhibitors and considerably lower than for nonselective COX inhibitors. This has been attributed mainly to the non-acidic chemical properties of nabumetone but also to its COX-1/COX-2 inhibitor profile. Through its metabolite 6-MNA, nabumetone has a dose-related effect on platelet aggregation, but no effect on bleeding time in clinical studies. Furthermore, several short-term studies have shown little to no effect on renal function. Compared with COX-2 selective inhibitors, nabumetone exhibits similar anti-inflammatory and analgesic properties in patients with arthritis and there is no evidence of excess GI or other forms of complications to date.
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PMID:Nabumetone: therapeutic use and safety profile in the management of osteoarthritis and rheumatoid arthritis. 1545 29

Nabumetone is a nonsteroidal antiinflammatory (NSAID) prodrug that inhibits cyclooxygenase-2. It has been recommended as a safe alternative in most patients with hypersensitivity reactions to NSAIDs. Systemic reactions caused by nabumetone are not frequent. We report 2 cases of immediate systemic reactions due to nabumetone. The first case involved a 68-year-old woman who developed immediate generalized pruritus, erythema, morbilliform eruption, swollen tongue sensation, diarrhea, and hypotension after the ingestion of a single dose of nabumetone. In the second case, a 77-year-old woman developed generalized pruritus, palm erythema, colic abdominal pain, diarrhea, dizziness, tightness of the chest, dyspnea, and hypotension immediately after oral intake of nabumetone. Both patients had previously tolerated this drug. Since these episodes, they have avoided nabumetone. Skin prick tests with nabumetone (10 and 100 mg/mL) were negative. Oral challenge tests with other NSAIDs, even of the same group as nabumetone, were negative in both patients. The mechanisms responsible for the reaction were not established.
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PMID:Severe immediate reaction to nabumetone. 1769 3

Although effective in the treatment of pain associated with rheumatic conditions such as osteoarthritis and rheumatoid arthritis, long-term use of NSAIDs is primarily limited by their association with upper gastrointestinal (GI) toxicity. Adverse effects range from dyspepsia and abdominal pain to ulceration and bleeding. GI damage elicited by NSAIDs arises as the result of biochemically induced topical irritant effects and by topical and systemic pharmacological suppression of gastroprotective prostaglandins. Variation in the physicochemical properties and pharmacological profiles among the individual NSAIDs translate into inter-agent differences regarding propensity to cause adverse GI effects. Nabumetone is a nonselective NSAID that offers distinct advantages over other agents in this class with regard to GI tolerability. Its non-acidic nature and pro-drug formulation, together with the lack of biliary secretion of its active metabolite, 6-methoxy-2-naphthylacetic acid, are thought to contribute to the improved GI tolerability of this drug. In head-to-head trials with other NSAIDs, nabumetone has demonstrated significant benefits regarding the incidence of GI events and more serious perforations, ulcers and bleeds (PUBs). Pooled data from eight postmarketing, randomized, controlled trials demonstrated a lower cumulative frequency of PUBs with nabumetone (0.03%; 95% CI 0.0, 0.08) versus comparator NSAIDs (1.4%; 95% CI 0.5, 2.4). Large-scale database studies also indicate that risk of serious GI complications is lower with nabumetone than comparator NSAIDs. Limited comparative data suggest that nabumetone offers a GI tolerability profile similar to that of cyclo-oxygenase-2 selective NSAIDs (coxibs). Although adverse cardiovascular outcomes appear to be a class effect of the coxibs, conventional NSAIDs may also have the potential for causing atherothrombotic complications. However, based on available data, nabumetone does not appear to be associated with increased cardiovascular risk. Finally, there is no particular concern about the nephrotoxic and hepatotoxic potential of nabumetone. Nonetheless, the potential for adverse drug reactions remains, and hence nabumetone, as with any NSAID, should be used at the lowest dose, which is effective for each patient, and for the shortest time necessary to control symptoms.
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PMID:Safety of the nonselective NSAID nabumetone : focus on gastrointestinal tolerability. 1848 83