china.com

AIM: The metabolites of naproxen produced by Cunninghamella species were isolated and identified, and further to compare the similarities between microbial transformation and mammalian metabolism. METHODS: Naproxen was transformed by three strains of Cunninghammella species (Cunninghamella blakeslesna AS 3.153, Cunninghamella echinulata AS 3.2004, and Cunninghamella elegans AS 3.156). The metabolites of naproxen were separated and assayed by liquid chromatography-mass spectrometry method. Semi-preparative HPLC was used to isolate the major metabolite, and the structure was identified by nuclear magnetic resonance (NMR) and mass spectrometry. RESULTS: Naproxen was transformed into 2 metabolites, desmethylnaproxen and desmethylnaproxen-6-O-sulfate, both were the known mammalian metabolites. The conjugated metabolite was newly detected in microbial transformation samples. CONCLUSION: The microbial transformation of naproxen has some similarities with the metabolism of naproxen in mammals. The fungi belonging to Cunninghamella species could be used as complementary in vitro models for drug metabolism to predict and produce the metabolites of drugs in mammals.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12740180&dopt=Abstract Naproxen Naprosyn





Pediatr Nephrol. 2003 Aug;18(8):826-9. Epub 2003 May 28.
Renal papillary necrosis induced by naproxen.

Kovacevic L, Bernstein J, Valentini RP, Imam A, Gupta N, Mattoo TK.

Division of Pediatric Nephrology, Children's Hospital of Michigan, 3901 Beaubien Boulevard, Detroit, MI 48201, USA.

A 17-year-old healthy girl was admitted to our hospital with diffuse abdominal pain and decreased oral intake of about 11 days duration. About a week prior to admission, she had taken naproxen, 250 mg four times a day for 4 days. Physical examination was normal except for diffuse abdominal tenderness on deep palpation. Investigations revealed high serum BUN (42 mg/dl) and creatinine (4.0 mg/dl). Serum electrolytes and complement (C3, C4) levels and urinalysis were normal. Antinuclear-antibody and anti-dsDNA were negative. Kidney biopsy revealed renal papillary necrosis, acute tubular necrosis, and focal interstitial nephritis. A diagnosis of nonoliguric acute renal failure due to naproxen nephrotoxicity was made. She received intravenous hydration, and oral steroids, which was gradually discontinued in 3 months. A follow-up at 4 months revealed normal renal function with a serum creatinine of 1.1 mg/dl, BUN 7 mg/dl, and normal urinalysis. The report highlights a need for caution while using naproxen or any other nonsteroidal anti-inflammatory drugs, even for a short duration.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12774222&dopt=Abstract Naproxen Naprosyn
[PubMed - in process]




Ann N Y Acad Sci. 2003 Mar;984:436-52.
Effect of immobilization site and membrane materials on multiphasic enantiocatalytic enzyme membrane reactors.

Li N, Giorno L, Drioli E.

Research Institute on Membrane Technology, ITM-CNR, University of Calabria, Rende (CS), Italy.

In the experimental work reported here the optical resolution of racemic naproxen methyl ester with crude lipase immobilized in a membrane reactor was studied. The multiphasic enantiocatalytic enzyme membrane reactor consisted of an organic phase that dissolved the naproxen methyl ester, a lipase-loaded membrane, and an aqueous phase that extracted the reaction product. Lipase preferentially converted the (S)-naproxen methyl ester to (S)-naproxen acid that was simultaneously separated by a membrane. The effect of the immobilization site and membrane type on the performance of the enzyme membrane reactor was studied. Capillary polyamide membrane with 10 kDa nominal molecular weight cutoff (NMWCO) and polysulfone membrane with 30 kDa NMWCO were applied, with lipase loaded in the sponge layer or on a membrane thin layer. With various immobilization sites and membrane types, the enzyme membrane reactors showed different productivity and enantioselectivity resulting from the varying amounts of immobilized enzyme and varying microenvironment of the hydrolysis reaction. Higher amounts of immobilized enzyme led to increased productivity and generally higher enantioslectivity of the membrane reactor. It seems that the location of organic/aqueous interface on membrane, which plays an important role in a multiphasic enzyme membrane reactor, was influenced by the immobilization site and membrane type and this affected the productivity and enantioselectivity. As much as 90% enantioexcess was obtained with a polyamide membrane, and lower values with a polysulfone membrane. A sponge layer of polyamide membrane is the preferred immobilization site for its higher productivity than a thin membrane layer, and for its higher enantioselectivity than a polysulfone membrane. In comparison with the unstable hydrolysis activity of free lipase in stirred tank reactor, a stable lipase activity can be obtained with the lipase-immobilized membrane reactor, irrespective of whether a polyamide or polysulfone membrane is used.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12783836&dopt=Abstract Naproxen Naprosyn


tulane.edu

A newly developed analytical method was used to measure concentrations of nine pharmaceuticals and personal care products (PPCPs) in samples from two surface water bodies, a sewage treatment plant effluent and various stages of a drinking water treatment plant in Louisiana, USA, and from one surface water body, a drinking water treatment plant and a pilot plant in Ontario, Canada. The analytical method provides for simultaneous extraction and quantification of the following broad range of PPCPs and endocrine-disrupting chemicals: naproxen; ibuprofen; estrone; 17beta-estradiol; bisphenol A; clorophene; triclosan; fluoxetine; and clofibric acid. Naproxen was detected in Louisiana sewage treatment plant effluent at 81-106 ng/l and Louisiana and Ontario surface waters at 22-107 ng/l. Triclosan was detected in Louisiana sewage treatment plant effluent at 10-21 ng/l. Of the three surface waters sampled, clofibric acid was detected in Detroit River water at 103 ng/l, but not in Mississippi River or Lake Pontchartrain waters. None of the other target analytes were detected above their method detection limits. Based on results at various stages of treatment, conventional drinking-water treatment processes (coagulation, flocculation and sedimentation) plus continuous addition of powdered activated carbon at a dosage of 2 mg/l did not remove naproxen from Mississippi River waters. However, chlorination, ozonation and dual media filtration processes reduced the concentration of naproxen below detection in Mississippi River and Detroit River waters and reduced clofibric acid in Detroit River waters. Results of this study demonstrate that existing water treatment technologies can effectively remove certain PPCPs. In addition, our study demonstrates the importance of obtaining data on removal mechanisms and byproducts associated with PPCPs and other endocrine-disrupting chemicals in drinking water and sewage treatment processes.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12826389&dopt=Abstract Naproxen Naprosyn





Int J Pharm. 2003 Jul 24;260(2):217-27.
Zinc-naproxen complex: synthesis, physicochemical and biological evaluation.

Sharma J, Singla AK, Dhawan S.

University Institute of Pharmaceutical Sciences, Punjab University, Chandigarh-160014, India.

Naproxen has a propensity to cause ulcers whereas zinc ions are known to possess an anti-ulcer and anti-inflammatory activity. Therefore, zinc complex of naproxen was prepared by adding zinc sulfate to an aqueous solution of sodium naproxen and its structure was characterized by IR, 1H NMR and 13C NMR, UV, DSC, atomic absorption spectroscopy, and elemental analysis. Anti-inflammatory studies, using the carrageenan-induced hind paw oedema showed that there was a significant difference (P<0.05, ANOVA plotted by Dunnet's test) in the anti-inflammatory activity of naproxen, its zinc complex, and the physical mixture of naproxen and zinc sulfate. In addition, zinc complex of naproxen showed a significant reduction in ulcers (lesion index (LI)) as compared to that of naproxen and physical mixture of naproxen and zinc sulfate. Thus, the use of the complex may be preferable to naproxen alone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12842341&dopt=Abstract Naproxen Naprosyn





Pharmazie. 2003 Jun;58(6):420-2.
Microbial transformations of S-naproxen by Aspergillus niger ATCC 9142.

He A, Rosazza JP.

Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242-5000, USA.

Aspergillus niger ATCC 9142 was used to catalyze the biotransformation of S(-)-naproxen (1) to three major metabolites that were isolated by solvent extraction, purified chromatographically, and characterized by mass spectrometry and NMR spectroscopy. Metabolites were identified as O-desmethylnaproxen (2), 7-hydroxynaproxen (3) and 7-hydroxy-O-desmethyinaproxen (4). The kinetics of naproxen biotransformation to 2 and 4 was established over an 84 h period to show that naproxen was completely metabolized at 36 h, the major metabolite was O-desmethylnaproxen at 24 h, and the 7-hydroxy-O-desmethylnaproxen that was formed after 24 h.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12857008&dopt=Abstract Naproxen Naprosyn


pru.ox.ac.uk

BACKGROUND: Naproxen and naproxen sodium are non-steroidal anti-inflammatory drugs used in a variety of painful conditions, including the treatment of postoperative pain. This review aims to assess the efficacy, safety and duration of action of a single oral dose of naproxen/naproxen sodium for moderate to severe acute postoperative pain in adults, compared with placebo. METHODS: The Cochrane Library (issue 4 2002), EMBASE, PubMed, MEDLINE and an in-house database were searched for randomised, double blind, placebo controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with acute postoperative pain. Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over 4 to 6 hours. Relative benefit and number-needed-to-treat were then calculated. The percentage of patients with any adverse event, number-needed-to-harm, and time to remedication were also calculated. RESULTS: Ten trials with 996 patients in met the inclusion criteria. Six trials compared naproxen sodium 550 mg (252 patients) with placebo (248 patients); the NNT for at least 50% pain relief over six hours was 2.6 (95% confidence interval 2.2 to 3.2). There was no significant difference between the number of patients experiencing any adverse event on treatment compared with placebo. Weighted mean time to remedication was 7.6 hours for naproxen sodium 550 mg (206 patients) and 2.6 hours for placebo (205 patients). Four other trials used lower doses. CONCLUSION: A single oral dose of naproxen sodium 550 mg is an effective analgesic in the treatment of acute postoperative pain. A low incidence of adverse events was found, although these were not reported consistently.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12964947&dopt=Abstract Naproxen Naprosyn
[PubMed - as supplied by publisher]