Arch Med Res. 1999 Mar-Apr;30(2):132-7.
Effect of superoxide dismutase from bovine erythrocytes on different activity parameters in adjuvant-induced arthritis.

Garcia-Gonzalez A, Herrera-Abarca J, Ochoa JL.

Departamento de Medicina Interna, Hospital General de Zona y Medicina Familar 1, Instituto Mexicano del Seguro Social, La Paz, Baja California Sur, Mexico.

BACKGROUND: The purpose of this work was to evaluate the effect of superoxide dismutase (SOD) on primary swelling, lipoperoxidation, body thymus, and spleen weight in the adjuvant-induced arthritis (AIA) model in rats. METHODS: Orally and intraperitoneally administered SOD (100 U/kg) from bovine erythrocytes, as well as naproxen (40 mg/kg) and dexamethasone (25 mg/kg), were evaluated against placebo. RESULTS: Primary edema was not decreased by SOD; in contrast, naproxen and dexamethasone showed good anti-inflammatory activity. Lipoperoxidation increased 1.8, 2.5, and 2.8 times with intraperitoneal SOD, naproxen, and dexamethasone administration, respectively, while oral SOD decreased lipoperoxidation levels to approximately one-half of that found in the control group. Body weight increased with SOD but decreased with dexamethasone. Naproxen did not change the animal weight. Thymus weight remained unchanged with SOD and naproxen, while it decreased with dexamethasone. Spleen weight remained the same with SOD, but increased with naproxen and decreased with dexamethasone. No side effects were observed in the SOD group, whereas 20% of the rats in the naproxen group died of gastrointestinal hemorrhage, and 50% of the rats in the dexamethasone group, of pulmonary infection. CONCLUSIONS: In conclusion, SOD showed no anti-inflammatory activity but decreased lipoperoxidation when administered orally. No deleterious effects in primary and secondary immunologic organs were observed with this agent.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10372448&dopt=Abstract Naproxen Naprosyn





Biotechnol Bioeng. 1999 Jul 5;64(1):120-6.
Lipase-catalyzed dynamic resolution of naproxen 2,2,2-trifluoroethyl thioester by hydrolysis in isooctane

Chang CS, Tsai SW, Kuo J.

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

A lipase-catalyzed enantioselective hydrolysis process under continuous in situ racemization of substrate by using trioctylamine as an organic base was developed for the production of (S)-naproxen from racemic naproxen thioesters in isooctane. Naproxen 2,2, 2-trifluoroethyl thioester and 45 degrees C were selected as the best substrate and temperature, respectively, by comparing the time-course variations for the racemization of (S)-naproxen thioesters containing an electron-withdrawing group. A detailed investigation of the effect of trioctylamine concentration on the kinetic behaviors of the thioester in racemization and enzymatic reaction was conducted, in which more than 70% conversion of the racemate (or 67.2% yield of (S)-naproxen) with eep value higher than 92% was obtained. Copyright 1999 John Wiley & Sons, Inc.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10397846&dopt=Abstract Naproxen Naprosyn
[PubMed - as supplied by publisher]




Pharmacotherapy. 1999 Jul;19(7):854-9.
Low-dose diclofenac, naproxen, and ibuprofen cohort study.

Perez-Gutthann S, Garcia-Rodriguez LA, Duque-Oliart A, Varas-Lorenzo C.

Global Epidemiology, Clinical Development, Novartis Pharmaceuticals, S.A., Barcelona, Spain.

The risk of a newly diagnosed episode of upper gastrointestinal bleeding, acute liver and renal failure, agranulocytosis, aplastic anemia, severe skin disorders, and anaphylaxis was examined within 30 days after the first prescription for a low dose of diclofenac, naproxen, or ibuprofen in a cohort in the United Kingdom. We identified 22,146 persons using diclofenac (< or = 75 mg), 46,919 using naproxen (< or = 750 mg), and 54,830 using ibuprofen (< or = 1200 mg). Age, gender, and comorbidity were similar in the three cohorts. Overall 64 potential cases were identified, and 20 were confirmed by medical record review. Incidence rates (95% CI) of upper gastrointestinal bleeding/10,000 people using diclofenac, naproxen, and ibuprofen were 1.8 (0.5-4.6), 2.3 (1.2-4.2), and 0.4 (0.04-1.3), respectively. There were three cases of hepatic injury, one with naproxen and two with ibuprofen. Although low, the incidence of gastrointestinal toxicity remains the main serious adverse event for all study drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10417034&dopt=Abstract Naproxen Naprosyn





Arthritis Rheum. 1993 Nov;36(11):1517-27.
Regulation of human normal and osteoarthritic chondrocyte interleukin-1 receptor by antirheumatic drugs.

Pelletier JP, McCollum R, DiBattista J, Loose LD, Cloutier JM, Martel-Pelletier J.

University of Montreal, Quebec, Canada.

OBJECTIVE. To determine the effect of antirheumatic drugs and corticosteroids on interleukin-1 receptor (IL-1R) levels in, and IL-1-stimulated metalloprotease synthesis and expression by, normal and osteoarthritic (OA) human articular chondrocytes. METHODS. IL-1R affinity and density of human chondrocytes were determined using radioligand binding experiments. Collagenase and stromelysin synthesis activities were analyzed by 14C-labeled type I collagen and Azocoll assays, respectively. Their messenger RNA (mRNA) levels were determined by Northern blot analysis. IL-1 alpha, IL-1 beta, IL-1 receptor antagonist, and beta 2-microglobulin were measured using enzyme-linked immunosorbent assays. Protein synthesis was determined by 3H-leucine incorporation. RESULTS. Antirheumatic drugs reduced the IL-1R level in normal and OA chondrocytes in a dose-dependent manner. In normal chondrocytes, tenidap reduced the IL-1R level by 44% at 5 micrograms/ml to 88% at 100 micrograms/ml (50% inhibition constant [IC50] 10.1 micrograms/ml), indomethacin reduced IL-1R by 6% at 1.5 micrograms/ml to 43% at 60 micrograms/ml, and naproxen reduced IL-1R by 10% at 10 micrograms/ml to 41% at 300 micrograms/ml; the effects observed with indomethacin and naproxen occurred only when the drugs were used at levels above their therapeutic concentrations. In OA chondrocytes, the effect of indomethacin and naproxen on the IL-1R level was greatly reduced, whereas tenidap still had a marked effect (IC50 22.5 micrograms/ml). Dexamethasone and hydrocortisone had no consistent effect on the IL-1R level. At a therapeutic concentration (20 micrograms/ml), tenidap was found to reduce the IL-1R level in a time-dependent manner, with maximum inhibition (98%) by 48 hours. Tenidap was also found to markedly reduce collagenase and stromelysin synthesis and mRNA levels in IL-1-stimulated chondrocytes. CONCLUSION. The suppressive effects of tenidap on IL-1-stimulated metalloprotease synthesis and expression in OA and normal chondrocytes are likely related to a decrease in IL-1R levels. At therapeutic concentrations, tenidap has a greater effect on the IL-1R level than is seen with indomethacin or naproxen, and glucocorticoids have no effect on IL-1R.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8240429&dopt=Abstract Naproxen Naprosyn


mwu.mukogawa-u.ac.jp

A uniform-sized molecularly imprinted polymer (MIP) for (S)-naproxen selectively modified with hydrophilic external layer has been prepared. First, the molecularly imprinted polymer for (S)-naproxen was prepared using 4-vinylpyridine and ethylene glycol dimethacrylate (EDMA) as a functional monomer and cross-linker, respectively, by a multi-step swelling and thermal polymerization method. Next, a 1:1 mixture of glycerol monomethacrylate (GMMA) and glycerol dimethacrylate (GDMA) was used for hydrophilic surface modification, and it was added directly to the molecularly imprinted polymer for (S)-naproxen 4 h after the start of molecular imprinting. The retention factors of all solutes tested were decreased with the surface modified molecularly imprinted polymer, compared with the unmodified molecularly imprinted polymer. However, chiral recognition of racemic naproxen was attained with the surface modified molecularly imprinted polymer as well as the unmodified molecularly imprinted polymer. Further, bovine serum albumin was completely recovered from the surface modified molecularly imprinted polymer. These results revealed that the chiral recognition sites of (S)-naproxen remained unchanged with hydrophilic surface modification, and that the molecularly imprinted polymer for (S)-naproxen was selectively modified with hydrophilic external layer. Preliminary results reveal that the surface modified molecularly imprinted polymer could be applicable to direct serum injection assays of (S)-naproxen.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10457431&dopt=Abstract Naproxen Naprosyn


uku.fi

PURPOSE: To synthesize and evaluate various novel aminoacyloxyalkyl esters of naproxen (3a-i) and naproxenoxyalkyl diesters of glutamic and aspartic acids (3j-m) as potential dermal prodrugs of naproxen. METHODS: The prodrugs 3a-m were synthesized, and their aqueous solubilities, lipophilicities and hydrolysis rates were determined in a buffered solution and in human serum. The permeation of selected prodrugs across excised postmortem human skin was studied in vitro. RESULTS: The aminoacyloxyalkyl prodrugs showed higher aqueous solubilities and similar lipid solubilities, in terms of octanol-buffer partition coefficients (log Papp) at pH 5.0, when compared with naproxen. At pH 7.4 the prodrugs were significantly more lipophilic than naproxen. Prodrugs 3a-i showed moderate chemical stability in aqueous solutions at pH 5.0 and were rapidly converted to naproxen in human serum (t1/2 = 4-19 min). The selected aminoacyloxyalkyl prodrugs possessed a higher flux across the skin than naproxen, with a maximum enhancement of 3-fold compared to naproxen. Prodrugs 3j-m showed poor aqueous solubility and permeation across the skin. CONCLUSIONS: Combinations of adequate aqueous solubility and lipophilicity of naproxen aminoacyloxyalkyl prodrugs having fast rates of enzymatic hydrolysis resulted in improved dermal delivery of naproxen.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10468016&dopt=Abstract Naproxen Naprosyn


mrl.oapi.com

BACKGROUND: Various animal models of non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulceration exist. These models have limitations, which make them less relevant to the human situation. AIM: : To develop a more simple and more relevant model of NSAID-induced gastric ulceration and adaptation. METHODS: Gastric ulceration was evaluated following the orogastric administration of naproxen (80 mg/kg b.d.) to hamsters. The effects of misoprostol and famotidine on gastric acid secretion and ulceration were also determined. Gastric adaptation was evaluated by proliferating cell nuclear antigen (PCNA) immunohistochemistry, in hamsters given naproxen for 3 weeks. Antral resistance to acute injury by NSAIDs and ethanol was also determined in these animals. RESULTS: Naproxen caused primarily gastric antral ulceration, which decreased from day 3 to day 21. This gastric adaptation was accompanied by an increase in PCNA positive cells, particularly on days 7 and 14. The adapted gastric antral mucosa was resistant to acute damage by various agents. Misoprostol (1 or 100 microg/kg) prevented antral ulceration, without affecting gastric acid secretion. Despite decreasing acid output by> 90%, famotidine (30 mg/kg) failed to prevent ulceration. CONCLUSION: The administration of naproxen (80 mg/kg b.d.) to hamsters is a simple, reliable and relevant method for evaluating NSAID-induced gastric antral ulceration and adaptation.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10571615&dopt=Abstract Naproxen Naprosyn