merck.com

BACKGROUND: Naproxen strongly inhibits platelet aggregation. OBJECTIVE: To examine the risk of acute thromboembolic cardiovascular events (TCEs) (myocardial infarction, sudden death, and stroke) with current naproxen use among patients with rheumatoid arthritis. METHODS: We studied patients aged 40 to 79 years with rheumatoid arthritis in the British General Practice Research Database, excluding those with a prior TCE and potentially confounding conditions. We matched up to 4 controls by sex, age, and site of medical practice to cases with first incident TCEs. The case diagnosis date was designated as the index date for each case and his or her controls. We categorized naproxen according to the most recent prescription prior to the index date as being current (< or =30 days), past (> 30 days but < 365 days), or none (> or =365 days before index date). Using conditional logistic regression, we conducted a matched case-control analysis with adjustment for potential confounders. RESULTS: We identified 809 cases. Current naproxen use was more common among controls (5.7%) than cases (3.2%). Adjusting for calendar year of treatment start, systemic corticosteroid use, diabetes, and comorbidity, we found that the odds ratio (95% confidence interval) for current naproxen use was 0.61 (0.39-0.94) while that for past use was 0.87 (0.65-1.16). Secondary and sensitivity analyses supported these results. CONCLUSIONS: In this case-control study, patients with rheumatoid arthritis and a current prescription for naproxen had a reduced risk of acute major TCEs relative to those with no naproxen prescription in the past year. These results are consistent with the ability of naproxen to inhibit platelet aggregation.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12020179&dopt=Abstract Naproxen Naprosyn


mcgill.ca

BACKGROUND: The association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acute myocardial infarction (AMI) is unclear. Nonsteroidal anti-inflammatory drugs vary in their antithrombotic properties, with naproxen having a particularly effective antithrombotic potential. OBJECTIVE: To compare the effect of naproxen vs other NSAIDs in the prevention of AMI in an older population. METHODS: Population-based, matched case-control study. Patients (aged > or =65 years) in Quebec had been hospitalized for AMI between January 1, 1992, and December 31, 1994. The admission date for AMI was considered the index date. Control subjects were randomly selected from a Quebec drug and physician claims database. For each case, a control was matched with the same index date, age (within 2 years), and sex. Cases and controls were required to have at least 1 year of pharmaceutical and medical records before the index date to identify risk factors for AMI and exposure to naproxen or other nonaspirin NSAIDs. Concurrent exposure to a medication was defined as exposure to that medication at the index date. Logistic regression analyses were used to evaluate the association between the use of naproxen and other NSAIDs in the prevention of AMI, adjusting for potential confounders. RESULTS: Included in the study were 4163 cases and 14 160 controls. Determinants (adjusted odds ratios [95% confidence intervals]) of AMI included use in the prior year of anticoagulants (0.76 [0.64-0.90]), nitrates (2.01 [1.86-2.17]), antidiabetic agents (1.72 [1.56-1.90]), antihypertensive agents (1.36 [1.28-1.45]), and lipid-lowering agents (0.83 [0.75-0.91]), as well as concurrent exposure to naproxen vs other NSAIDs (0.79 [0.63-0.99]). CONCLUSION: Compared with other NSAIDs, concurrent exposure to naproxen has a protective effect against AMI.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12020180&dopt=Abstract Naproxen Naprosyn


merck.com

BACKGROUND: Etoricoxib is a highly selective COX-2 inhibitor which was evaluated for the treatment of rheumatoid arthritis (RA). METHODS: Double-blind, randomized, placebo and active comparator-controlled, 12-week study conducted at 67 sites in 28 countries. Eligible patients were chronic NSAID users who demonstrated a clinical worsening of arthritis upon withdrawal of prestudy NSAIDs. Patients received either placebo, etoricoxib 90 mg once daily, or naproxen 500 mg twice daily (2:2:1 allocation ratio). Primary efficacy measures included direct assessment of arthritis by counts of tender and swollen joints, and patient and investigator global assessments of disease activity. Key secondary measures included the Stanford Health Assessment Questionnaire, patient global assessment of pain, and the percentage of patients who achieved ACR20 responder criteria response (a composite of pain, inflammation, function, and global assessments). Tolerability was assessed by adverse events and routine laboratory evaluations. RESULTS: 1171 patients were screened, 891 patients were randomized (N = 357 for placebo, N = 353 for etoricoxib, and N = 181 for naproxen), and 687 completed 12 weeks of treatment (N = 242 for placebo, N = 294 for etoricoxib, and N = 151 for naproxen). Compared with patients receiving placebo, patients receiving etoricoxib and naproxen showed significant improvements in all efficacy endpoints (p<0.05). Treatment responses were similar between the etoricoxib and naproxen groups for all endpoints. The percentage of patients who achieved ACR20 responder criteria response was 41% in the placebo group, 59% in the etoricoxib group, and 58% in the naproxen group. Etoricoxib and naproxen were both generally well tolerated. CONCLUSIONS: In this study, etoricoxib 90 mg once daily was more effective than placebo and similar in efficacy to naproxen 500 mg twice daily for treating patients with RA over 12 weeks. Etoricoxib 90 mg was generally well tolerated in RA patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12033987&dopt=Abstract Naproxen Naprosyn
[PubMed - as supplied by publisher]




Arzneimittelforschung. 2002;52(4):294-301.
Effect of combined chemotherapy and anti-inflammatory drugs on murine schistosomiasis.

Mahmoud MR, Zoheiry MM, Nosseir MM.

Department of Pharmacology, Theodor Bilharz Research Institute, Imbaba, Guiza, Egypt.

Hepatic granulomas resulting from Schistosoma mansoni infection contain high levels of prostaglandins (PG) and leukotrienes. The present experimental study was conducted to show the effect of murine S. mansoni infection on PGE2 level in the liver granuloma homogenate and to explore the possibility of using non-steroidal anti-inflammatory drugs (NSAIDs) namely, ibuprofen (CAS 15687-27-1) and naproxen (CAS 22204-53-1), either alone or in combination with praziquantel (CAS 55268-74-1) to induce regression of hepatic morbidity or to ameliorate the biochemical and histopathological consequences and intensity of infection. Infection with S. mansoni increased the level of alanine amino-transaminase (ALT), gamma glutamyl transferase (GGT), PGE2, hepatic collagen deposition, antibody titre and circulating schistosomal antigen. The last parameter was reduced significantly by progression of infection in the 11th and 16th weeks. Treatment with praziquantel was found to reduce the number of worms (97%), with complete absence of immature ova and increase in the number of dead ova. Also it reduced all the elevated parameters except PGE2. NSAIDs were found to reduce significantly the level of PGE2 at 9 weeks but not at 11 and 16 weeks post-infection. ALT and GGT were not significantly decreased compared to their corresponding controls. Treatment with ibuprofen or naproxen either alone or in combination with praziquantel or praziquantel alone reduced significantly the granuloma diameters. Collagen deposition and percentage of fibrotic area were significantly decreased compared to infected control but the antibody titre or circulating antigen levels were not affected. Combined therapy of praziquantel with ibuprofen or naproxen improved most of the parameters estimated and maintained the reducing effect on PGE2 at 11 and 16 weeks post-infection. So it can be concluded that in S. mansoni infection treatment with ibuprofen or naproxen is not preferable without treatment of schistosomiasis by using praziquantel.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12040972&dopt=Abstract Naproxen Naprosyn


farmfi.scifarm.unifi.it

Ground mixtures of naproxen with amorphous beta-cyclodextrin-epichlorohydrin soluble (betaCd-EPS) or insoluble cross-linked (betaCd-EPI) polymers were investigated for both solid phase characterization (Differential Scanning Calorimetry, powder X-ray Diffractometry) and dissolution properties (dispersed amount method). The effect of different grinding conditions and of drug-to-carrier ratio was also evaluated. Co-grinding induced a decrease in drug crystallinity to an extent which depended on the grinding time, and was most pronounced for the cross-linked insoluble polymer, particularly in combinations at the lowest drug content. Both cyclodextrin polymers were more effective in improving the naproxen dissolution properties, not only than the parent betaCd but also than hydroxyalkyl-derivatives, and their performance was almost comparable to that of methyl-derivatives, previously found as the best carriers for naproxen. Dissolution efficiencies of naproxen from physical mixtures with betaCd-EPS, thanks to the high water solubility of this Cd-derivative, were up to three times higher than those from the corresponding products with betaCd-EPI. However this difference in their performance became much less evident in co-ground products and tended to progressively diminish with increasing the polymer content in the mixture, according to the better amorphizing power shown by betaCd-EPI during the co-grinding process. The 10/90 (w/w) drug-carrier co-ground products exhibited the best dissolution properties, giving dissolution efficiencies about 30 times higher than that of naproxen alone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12110386&dopt=Abstract Naproxen Naprosyn





Biotechnol Bioeng. 2002 Jul 20;79(2):200-10.
Integration of reactive membrane extraction with lipase-hydrolysis dynamic kinetic resolution of naproxen 2,2,2-trifluoroethyl thioester in isooctane.

Lu CH, Cheng YC, Tsai SW.

Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China.

Lipases immobilized on polypropylene powders have been used as the biocatalyst in the enantioselective hydrolysis of (S)-naproxen from racemic naproxen thioesters in isooctane, in which trioctylamine was added to perform in situ racemization of the remaining (R)-thioester substrate. A detailed study of the kinetics for hydrolysis and racemization indicates that increasing the trioctylamine concentration can activate and stabilize the lipase as well as enhance the racemization and non-stereoselective hydrolysis of the thioester. Effects of the aqueous pH value and trioctylamine concentration on (S)-naproxen dissociation and partitioning in the aqueous phase as well as the transportation in a hollow fiber membrane were further investigated. Good agreements between the experimental data and theoretical results were obtained when the dynamic kinetic resolution process was integrated with a hollow fiber membrane to reactively extract the desired (S)-naproxen out of the reaction medium. Copyright 2002 Wiley Periodicals,

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12115436&dopt=Abstract Naproxen Naprosyn


cc.kmu.edu.tw

A water-soluble polymeric prodrug containing a naproxen moiety was synthesized. The carboxylic groups of naproxen were condensed with the hydroxyl groups of 2-hydroxyethyl methacrylate (HEMA) to produce a drug-linked monomer, denoted HN. The polymeric prodrug was prepared by copolymerization of HN with methacrylic acid. The molar percentage of HN in the polymeric prodrug was 26 mol%, as determined by 1H NMR. To investigate the pertinence of this polymeric prodrug, the hydrolysis was studied in-vitro with or without esterase or lipase. The kinetics of enzymatic catalysis was calculated from a Lineweaver-Burk plot. The anti-inflammatory activity was evaluated using the carrageenan-induced oedema test. The polymeric prodrug released a major fraction of the free naproxen and a significant fraction of the hydroxyethyl ester derived-naproxen. The maximum hydrolysis rate Vmax, and the Michaelis constant Km were calculated to be 2.16 x 10(-5) equiv. mol L-1 min-1 and 5.11 x 10(-2) equiv. mol L-1. The maximum anti-inflammatory inhibition of free naproxen appeared at 2 h and quickly decreased thereafter. In contrast, the polymeric prodrug showed a maximum at around 2-3 h and then slowly decreased. This indicates that the polymeric prodrug displays greater potency than free naproxen in the inhibition of acute inflammatory processes over long periods.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12195829&dopt=Abstract Naproxen Naprosyn