Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new relafen research articles will be listed here shortly after becoming available to us.
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Medical research on relafen
Biomed Chromatogr. 2008 Jul 23;
Patel BN, Sharma N, Sanyal M, Prasad A, Shrivastav PS
A simple, precise and accurate assay for the determination of 6-methoxy-2-naphthylacetic acid (6-MNA), an active metabolite of nabumetone in human plasma, was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The analyte (6-MNA) and propranolol (internal standard, IS) were extracted from 200 microL aliquot of human plasma via solid-phase extraction employing HLB Oasis cartridges and separated on a Discovery((R)) HS C(18) (50 x 4.6 mm, 5 microm) column. Detection of analyte and IS was done by tandem mass spectrometry with a turbo ion spray interface operating in positive ion and multiple reaction monitoring acquisition mode. The total chromatographic runtime was 3.0 min with retention time for 6-MNA and IS at 1.97 and 1.26 min, respectively. The method was validated over a dynamic linear range of 0.20-60.00 microg/mL for 6-MNA with mean correlation coefficient r >/= 0.9986. The intra-batch and inter-batch precision (%CV) across five validation runs (lower limit of quantiation, low-, medium- and high-quality controls and upper limit of quantitation) was less than 7.5%. The accuracy determined at these levels was within -5.8 to +0.2% in terms of percentage bias. The method was successfully applied for a bioequivalence study of 750 mg nabumetone tablet formulation in 12 healthy Indian male subjects under fasted condition. Copyright (c) 2008 John Wiley & Sons, Ltd.
Retina. 2008 Jul 14;
Pastor J, Del Nozal MJ, Zamarron E, García M
PURPOSE:: To determine, in vitro, the solubility in silicone oil (SO) of triamcinolone acetonide, dexamethasone, and some nonsteroideal antiinflammatory drugs including phenylbutazone and nabumetone. METHODS:: Antiinflammatory drugs were initially dissolved in organic solvents (chloroform or diethyl ether). The solubilized drugs were then added to 1,000 centipoise purified SO to yield final concentrations that were therapeutically relevant. The degree of solubilization was judged by the transparency of the final mixture. The kinetics of phenylbutazone diffusion from SO into water were measured for 30 days by derivative spectrophotometry. RESULTS:: Most of the tested drugs, including triamcinolone acetonide, were not soluble in SO. Only phenylbutazone and nabumetone, each at 80 mug/mL, were soluble in SO. The release of phenylbutazone from SO into water over a 30 day period followed zero order kinetics during the first 15 days. CONCLUSION:: Triamcinolone acetonide and most other antiinflammatory drugs tested are not soluble in SO. This fact must be taken into consideration when using these drugs in combination with SO.
Safety of the nonselective NSAID nabumetone : focus on gastrointestinal tolerability.
Drug Saf. 2008; 31(6): 485-503
Bannwarth B
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.
Int J Pharm. 2008 Jun 24; 358(1-2): 303-6
Crothers M, Ricardo NM, Heatley F, Nixon SK, Attwood D, Booth C
The solubilisation of two poorly soluble drugs, furosemide and nabumetone, in micellar solutions of diblock copolymers of ethylene oxide and styrene oxide has been studied at 25 and 37 degrees C and solubilisation capacities compared with published values for griseofulvin and docetaxel. Solubilisation in the micelle core, corrected for the different proportions of poly(styrene oxide) in the copolymers, was similar for all four drugs. The highest solubilisation capacities were found for a copolymer with worm-like micelles.
Afr J Med Med Sci. 2007 Sep; 36(3): 249-57
Adegoke AO, Idowu SO, Olaniyi AA
A novel colorimetric determination ofnabumetone in tablets has been developed. The assay is based on chemical derivatization (aromatic ring derivatization technique) using newly developed 4-carboxyl-2,6-dinitrobenzene diazonium (CDNBD) ion as the chromogenic derivatizing reagent and resultant formation of azo dye.Optimization studies established an optimal reaction time of 10 minutes at 30 degrees C after mixing the drug/reagent mixture in a vortex mixer for 10 sec. A new absorption maximum (ë(max)) was found at 470 nm, which was selected as analytical wavelength. The assays were linear over 1-6 microg/ml of nabumetone and the optimal reaction required a 2:1 reagent/drug stoichiometric ratio.The developed method has a low limit of detection of 0.39 microg/ml, and is reproducible (1.81% RSD). It has been applied successfully to the assay of nabumetone tablets and is of equivalent accuracy (p > 0.05) with the official (B.P) HPLC method. The new method is simple, has the main advantage of employing a more affordable instrumentation and could find application in routine in-process quality control of nabumetone tablets.
J Fluoresc. 2008 Sep; 18(5): 973-7
Rodrigues MR, Lima A, Codognoto L, Villaverde AB, Tavares Pacheco MT, Moisés de Oliveira HP
The microenvironment formed by lauroyl and stearoyl derivatives of chitosan in solution has been studied using two fluorescent probes, pyrene and nabumetone. Existence or not of microdomains formed by polymolecular associations, the inherent hydrophobicity of them in aqueous solution, and the influence of degree of substitution (DS) of derivatives were investigated by emission properties of pyrene and strengthened by the photophysical behavior of nabumetone. Additionally, the ratio between the fluorescence intensities of first (~372 nm) to the third (~384 nm) bands of the emission spectrum of pyrene was used to determine the critical aggregation concentration (CAC). In a previous work, it was already reported the characterization of chitosan derivatives by three spectroscopic techniques ((13)C-NMR, (1)H-NMR and infrared), as well as data on the solubility and swelling-index of them. In addition of that, the new results show that the investigated lauroyl and stearoyl derivatives of chitosan are expected to be potential models for applications in the medical field.
Curr Med Res Opin. 2007 Oct; 23(10): 2395-404
Morrison A, Ramey DR, van Adelsberg J, Watson DJ
OBJECTIVE: To investigate the effects of continued use of non-selective NSAIDs (nsNSAIDs) on blood pressure and hypertension. RESEARCH DESIGN AND METHODS: This was a systematic review of randomized clinical trials of oral nsNSAIDs used for at least a 4-week duration. Searches were conducted of PubMed and the Cochrane Database of Systematic Reviews, using key terms for nsNSAIDs and blood pressure or hypertension, to identify articles published in the English language peer-reviewed literature through March 2007. MAIN OUTCOME MEASURES: Change from baseline to end of study in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and the incidence of hypertension. Pooled statistics were computed using fixed and random-effects analyses. RESULTS: Thirty-two articles were included. The mean change (95% confidence interval [CI]) in blood pressure (in mmHg) from baseline to end of study for five trials of ibuprofen was 3.54 (2.70, 4.39) for SBP and 1.16 (0.68, 1.64) for DBP (p < 0.001 for both changes). Results of four trials of indomethacin were similar to those for ibuprofen: 2.90 (-0.28, 6.08) for SBP (p = 0.07) and 1.58 (0.29, 2.87) for DBP (p = 0.02). Mean changes from baseline for two trials of diclofenac were -0.46 (-1.48, 0.56) for SBP (p = 0.38) and -0.56 (-1.19, 0.07) for DBP (p = 0.08) and were similar to those for placebo. Changes from baseline in SBP were positive but not statistically significant for naproxen, sulindac, and nabumetone. Compared with placebo, the risk ratio (95% CI) for hypertension was 2.85 (1.44, 5.65; p = 0.003) in two ibuprofen trials. CONCLUSIONS: Continued use of ibuprofen increases blood pressure and raises the incidence of hypertension. There appears to be heterogeneity in such effects with continued use of other nsNSAIDs but, due to limitations in the data, results for naproxen, sulindac, and nabumetone are inconclusive.
Effect of polymer molecular weight on the production of drug nanoparticles.
J Pharm Sci. 2007 Oct; 96(10): 2655-66
Sepassi S, Goodwin DJ, Drake AF, Holland S, Leonard G, Martini L, Lawrence MJ
Stable, polymer-coated nanoparticles of two hydrophobic drugs, namely nabumetone and halofantrine, have been prepared by a wet-bead milling process performed in the presence of a stabilizing homopolymer, either hydroxypropylmethylcellulose (HPMC) or polyvinylpyrrolidone (PVP), of differing molecular weights and concentrations. Although nabumetone nanoparticles could only be produced when HPMC was used as stabilizing polymer, halofantrine nanoparticles could be prepared using either HPMC or PVP. Stable nanoparticles of nabumetone could be produced using a HPMC solution of viscosity average molecular weight, M(v), of 5 kg/mol over an approximate four fold polymer concentration range (0.63-2.5% w/w) when a drug loading of 20% w/w was used. Increasing the molecular weight of HPMC up to a limiting M(v) of 89 kg/mol did not result in the formation of nanoparticles at any of the polymer concentrations examined. The amount of polymer absorbed onto the nanoparticles was determined by measuring the depletion of polymer from solution based on either an ultra-violet (PVP) or optical rotatory dispersion (ORD) (HPMC) assay. The slightly lower concentration of HMPC found to be present on the surface of the halofantrine nanoparticles compared with the nabumetone nanoparticles suggested a differing affinity of the polymer for the surface of the two drugs.
Severe immediate reaction to nabumetone.
J Investig Allergol Clin Immunol. 2007; 17(4): 274-6
Gonzalo-Garijo MA, Cordobés-Duran C, Lamilla-Yerga AM, Moreno-Gastón I
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.
Cochrane Database Syst Rev. 2006; CD000142
Watson M, Brookes ST, Faulkner A, Kirwan J
BACKGROUND: Osteoarthritis(OA) is the most common rheumatic disease. Simple analgesics are now accepted as the appropriate first line pharmacological treatment of uncomplicated OA. Non-aspirin NSAIDs are licensed for the relief of pain and inflammation arising from rheumatic disease. OBJECTIVES: To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of osteoarthritis (OA) of the knee. SEARCH STRATEGY: We searched Medline (1966-1995) and Bids Embase (Jan-Dec, 1980-1995). The searches were limited to publications in the English language, and were last performed in November 1996. We used modified Cochrane Collaboration search strategy to identify all randomised controlled trials. The MeSH heading "osteoarthritis" was combined with the generic names of the 17 non-aspirin NSAIDs licensed in the UK for the management of OA in general practice. The search of Embase used the term "osteoarthritis" if present in the abstract, title or keywords, and was combined with the generic names of the 17 non-aspirin NSAIDs, only if they were mentioned in the title, abstract or keywords. SELECTION CRITERIA: All double blind, randomised controlled trials, in the English language, comparing the efficacy of two non-aspirin NSAIDs in the management of osteoarthritis of the knee, were selected. Only trials with subjects aged 16 years and over, with clinical and/or radiological confirmation of the diagnosis of OA knee were included. Studies which compared one "trial" NSAID with one "reference" NSAID were included provided they were non-aspirin NSAIDs available in the UK and were licensed for the treatment of OA by general practitioners. Trials which were placebo-controlled and which also involved the comparison of two NSAIDs were also included. DATA COLLECTION AND ANALYSIS: The methodological design of each study was scored according to a pre-determined system. The three main outcome measures of pain, physical function and patient global assessment were chosen based on the core set agreed upon by OMERACT (Outcome Measures in Rheumatology Clinical Trials). These were used to determine the power of each trial. The equivalency of NSAID doses was calculated using the percentage of the recommended maximum daily dose. Sample size estimates for the detection of clinically relevant changes in outcome measures used in the assessment of OA knee were used for power calculations. These calculations were performed to determine whether the trials were of a sufficient size to detect clinically relevant differences which were statistically significant. The calculations incorporate estimates of standard deviation, and minimum, median and maximum differences (delta) between drugs which are deemed to be clinically important. The number of "withdrawals due to lack of efficacy" was also selected as an outcome measure for this review. The Peto odds ratio and 95% confidence intervals were calculated where possible. The results of studies which compared the same trial and reference NSAIDs were combined where possible. MAIN RESULTS: Of the 1151 trials identified by the search strategy, 22 involved knee osteoarthritis only. Sixteen of these trials fulfilled the inclusion criteria and were entered in the review. Eight NSAIDs were represented in these trials. Etodolac was represented in 11 trials. The reference NSAID in these trials was piroxicam (n=3), naproxen(n=3), diclofenac (n=3), indomethacin (n=1), and, nabumetone (n=1).The reported methodological design of the trials was poor, with a median score of 3 (out of a maximum of 8).The results of the trials comparing the same trial and reference NSAIDs were pooled for the outcome "withdrawal due to lack of efficacy". For the comparison, etodolac versus piroxicam, the odds ratio favoured etodolac i.e. patients receiving etodolac were less likely to withdraw due to lack of efficacy. The dose of etodolac used in each of these three studies, however, was greater than the corresponding dose of piroxicam (based on percentage maximum daily dose). The significance of these results is therefore questionable. For the comparisons etodolac versus diclofenac, and etodolac versus naproxen, there were no clear differences between treatments. In one study [Bellamy 1993], a statistically significant difference was detected between treatments with regard to withdrawals due to lack of efficacy. In this trial, which compared equivalent NSAID doses, diclofenac was the favoured NSAID compared to tenoxicam(p=0.04).Two studies showed a statistical difference in patient global assessment of condition, which favoured the trial NSAID. In both cases the trial NSAID was etodolac, used in doses approximately 25-44% greater than the reference NSAID. Two studies showed a statistically significant difference in pain relief between NSAIDs. The trial NSAID in both cases was again etodolac but the doses exceeded those of the reference NSAIDs. AUTHORS' CONCLUSIONS: In spite of the large number of publications in this area, there are few randomized controlled trials. Furthermore, most trials comparing two or more NSAIDs suffer from substantial design errors. From the results of this review it is concluded that no substantial evidence is available related to efficacy, to distinguish between equivalent recommended doses of NSAIDs. Had studies employed appropriate doses of comparator drug, most would have been sufficiently powerful to detect clinically important differences in efficacy. As differences in efficacy between NSAIDs have not been recorded, the selection of an NSAID for prescription for OA knee should be based upon relative safety, patient acceptability and cost.