USAL.ES

The aim of this study was to investigate the effect of the presence of the water-soluble polymer polyethylene glycol (PEG)-MW=35000 g/mol-on the complexation of the phototoxic anti-inflammatory drug naproxen, in its sodium salt form, with beta-cyclodextrin (beta-CD). The data revealed that the polymer does not interact with the uncomplexed naproxen whereas it does with the beta-CD.The presence of different proportions of PEG, in the 0-1% (w/w) range, systematically lowers K(app) of the formation of the naproxen:beta-CD inclusion complex. The reason for the decrease in the complexed drug is the presence of other competing equilibria, the first one is an interaction of the polymer with the beta-CD, which in turn reduces the amount of free CD available for including the naproxen, and the second is the formation of a naproxen:beta-CD:PEG ternary complex with lower affinity than the binary complex. The binding constant of these processes are K(2)=(4.5+/-1.0) x 10(5) M(-1) and K(3)=870+/-19 M(-1), respectively.In addition the presence of the PEG produces an important change in the driving force of the complex formation. In this case the process is enthalpically unfavoured and entropically favoured; these are typical characteristics of processes governed by hydrophobic interactions.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14522127&dopt=Abstract Naproxen Naprosyn





Cancer Lett. 2003 Nov 25;201(2):139-48.
Naproxen, clenbuterol and insulin administration ameliorates cancer cachexia and reduce tumor growth in Walker 256 tumor-bearing rats.

Piffar PM, Fernandez R, Tchaikovski O, Hirabara SM, Folador A, Pinto GJ, Jakobi S, Gobbo-Bordon D, Rohn TV, Fabricio VE, Moretto KD, Tosta E, Curi R, Fernandes LC.

Laboratorio de Metabolismo Celular, Departamento de Fisiologia, Setor de Ciencias Biologicas, Universidade Federal do Parana, Centro Politecnico, Jd. das Americas, Curitiba-Pr 81530-990, Brazil.

Cancer cachexia is characterized by anorexia and intense peripheral catabolism. We examine the potential benefits of combination of different anabolic agents such as insulin and clenbuterol associated to prostaglandin synthesis inhibitor (naproxen) on tumor growth, cachexia and renal function in Walker 256 tumor-bearing rats (WK). Groups were separated into WK, and WK with naproxen (WK N) or naproxen plus clenbuterol (WK NCb) or naproxen plus clenbuterol plus insulin (WK NCbI). Treatment begins at the 4th day after tumor inoculation, at the 14th day they were killed, glycemia, lacticidemia, glycogen content from liver, soleus and gastrocnemius muscles, tumor mass, body weight and kidney function were determined. Glycemia and glycogen content were reduced and lacticidemia increased in WK (p<0.05) as compared to control rats. The glycogen content recovered in all treated groups. Tumor weight was significantly reduced by the different treatments. At the 14th weight change (carcass-initial body weight) in the control increased by 38% and in the WK -2%. Naproxen treatment (WK N) induced an increased by 14%. The inclusion of clenbuterol (WK NCb) and insulin (WK NCbI) by 38 and 41%, respectively. Mean glomerular filtration rate (GFR) increased in the WK (p<0.05) as compared to control, but in the WK NCb the GFR was similar to control. Our results suggest that naproxen is able to reduce tumor growth and its association with insulin and clenbuterol induce mass weight gain and recovery energy fuel.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14607327&dopt=Abstract Naproxen Naprosyn





Eur Spine J. 2003 Nov 21 [Epub ahead of print]
Acute phase response in patients undergoing lumbar spinal surgery: modulation by perioperative treatment with naproxen and famotidine.

Munoz M, Garcia-Vallejo JJ, Sempere JM, Romero R, Olalla E, Sebastian C.

GIEMSA, Department of Biochemistry, School of Medicine, University of Malaga, Malaga, Spain.

In orthopaedic surgery, perioperative administration of non-steroidal anti-inflammatory drugs has been shown to reduce postoperative pain and analgesic consumption. In addition, preoperative administration of ibuprofen has proved to reduce interleukin-6 (IL-6) release, while that of ranitidine reduced postoperative IL-6-induced C-reactive protein synthesis in patients undergoing abdominal surgery. However, it has not been established whether the preoperative administration of both types of drugs may reduced the postoperative inflammatory reaction after instrumented spinal surgery. Accordingly, our objective was to investigate the effects of preoperative treatment with naproxen plus famotidine on the postoperative systemic inflammatory reaction in patients undergoing instrumented lumbar spinal surgery. Forty consecutive patients scheduled for elective instrumented spinal fusion were alternately assigned to receive either naproxen (500 mg/day, p.o.) plus famotidine (40 mg/day, p.o.) for 7 days before operation, or no adjuvant treatment. Haematological parameters, acute phase proteins, complement fractions, immunoglobulins and cytokines were determined 7 days and immediately before surgery, and on days 0, 1, 2 and 7 after surgery. Haematological parameters, clinical data, duration of surgery, blood loss, perioperative blood transfusion and postoperative complications were similar in the two groups, although pretreated patients showed lower increases in body temperature and required less analgesic medication. Compared with preoperative levels, IL-6 levels were significantly increased postoperatively in all patients with no differences between groups. C-reactive protein, alpha(1)-acid-glycoprotein and haptoglobin levels were also significantly increased postoperatively in all patients; however, they were significantly lower in pretreated patients. In conclusion, perioperative treatment with naproxen plus famotidine was well tolerated and reduced the acute phase response after instrumented spinal surgery. However, further research is needed to determine the best dose and timing of preoperative treatment administration, and to correlate these changes with long-term clinical results.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14634855&dopt=Abstract Naproxen Naprosyn
[PubMed - as supplied by publisher]

turk.net

A total of 105 patients with established fixed drug eruption (FDE) by oral provocation were evaluated with regard to a drug-related site involvement. Cotrimoxazole was the leading causative agent (63.8%), followed by naproxen sodium (23.8%), dipyrone (5.7%), oxicams (4.8%) and other rare causes (1.9%). Cotrimoxazole most frequently induced lesions on genital mucosa; naproxen and oxicams on lips; and dipyrone on trunk and extremities. Isolated FDE on male genitalia (n = 16) was exclusively because of cotrimoxazole. A highly significant association could be established between naproxen and FDE on lips (chi-square = 28.3; corrected P =.000002). As this study represents the largest series of patients with naproxen-induced FDE, we would suggest that naproxen should be considered as an important potential cause of FDE on lips.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14639376&dopt=Abstract Naproxen Naprosyn


superonline.com

OBJECTIVES: To investigate the efficacy of single daily doses of rofecoxib, a selective inhibitor of cyclooxygenase-2, in dysmenorrhea. METHODS: Fifty-five patients were included in this randomized, placebo-controlled, cross-over study. Patients were randomized to use placebo, naproxen sodium (550 mg), 25 and 50 mg doses of rofecoxib in various orders. Pain intensity, analgesic efficacy of drugs, total number of pills used and side effects were evaluated. RESULTS: Rofecoxib with daily single doses of 25 and 50 mg decreased the pain intensity in a manner similar to naproxen sodium. Most of the patients (85.45% and 96.46%) evaluated the analgesic efficacy of rofecoxib as 'perfectly effective'. Rofecoxib was found to be effective for pain relief both in primary and secondary dysmenorrhea. Gastrointestinal adverse effects were less than those with naproxen sodium. CONCLUSIONS: A 'one a day' dose of 25 mg rofecoxib is an effective choice with lower gastrointestinal adverse effects than naproxen sodium.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14643039&dopt=Abstract Naproxen Naprosyn
[PubMed - in process]




Can J Physiol Pharmacol. 1985 Jul;63(7):798-803.
Effect of nonsteroidal anti-inflammatory drugs on the microsomal monooxygenase system of rat liver.

Belanger PM, Atitse-Gbeassor A.

The effect of acetylsalicylic acid, ibuprofen, indomethacin, ketoprofen, naproxen, phenylbutazone, and salicylic acid on the microsomal oxidative drug metabolism of rat liver was studied. Pretreatment of the rats with pharmacologic doses of acetylsalicylic acid, indomethacin, and ketoprofen decreased both the demethylase and hydroxylase activities of rat liver microsomes. These effects were paralleled by decreases in microsomal cytochrome P-450 content. The rate of the microsomal reactions was increased after pretreatment with ibuprofen and naproxen but only the former increased the concentration of cytochrome P-450. Phenylbutazone and salicylic acid had no in vivo effect on the hepatic monooxygenase. The addition of 1 mM of ibuprofen, indomethacin, ketoprofen, naproxen, and phenylbutazone to rat liver microsomes inhibit both the aminopyrine N-demethylase and p-nitro-anisole O-demethylase activities. The extent of the inhibition varied between 21 and 73% of the control incubation. Indomethacin, naproxen, and phenylbutazone also decreased the aniline hydroxylase activity to roughly 60% of the control value. Acetylsalicylic acid and salicylic acid had no in vitro effect on the microsomal monooxygenase. The nonsteroidal anti-inflammatory drugs produced a reverse type I binding spectrum with oxidized cytochrome P-450; indomethacin and phenylbutazone were the strongest ligands. There is no correlation between the effect of addition of nonsteroidal anti-inflammatory drugs to the hepatic microsomal homogenate and their in vivo effect on the monooxygenase activity.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=4042014&dopt=Abstract Naproxen Naprosyn





Am J Gastroenterol. 2003 Dec;98(12):2627-34.
Incidence of outpatient physician claims for upper gastrointestinal symptoms among new users of celecoxib, ibuprofen, and naproxen in an insured population in the United States.

Goldstein JL, Zhao SZ, Burke TA, Palmer R, von Allmen H, Henderson SC.

Department of Medicine, Section of Digestive Diseases and Nutrition, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.

OBJECTIVE: The aim of this study was to compare the risk of outpatient medical claims for UGI symptoms among new users of celecoxib versus ibuprofen, and naproxen. METHODS: The study was conducted using LifeLink, an insurance claims database of approximately 1.8 million employees, dependents, and retirees in the United States. Patients newly treated with a prescription of celecoxib, ibuprofen, or naproxen between June 1, 1999, and June 30, 2001, were included. A patient with an upper GI (UGI) symptom was any individual with an outpatient physician claim for dyspepsia (ICD-9 = 536.8), abdominal pain (789.0), or nausea/vomiting (787.0). Incidence was determined using person-time analysis. Multivariate analyses were conducted using Poisson and Cox regression models. RESULTS: The cohort consisted of patients prescribed celecoxib (n = 68,939), ibuprofen (n = 71,456), or naproxen (n = 50,014). At baseline, celecoxib users were older and more likely to have a history of UGI or cardiovascular conditions. The incidence rate of any UGI symptom was 0.46 per 1,000 patient-days for celecoxib, 0.70 for ibuprofen, and 0.62 for naproxen. After adjusting for confounding factors using Poisson regression, the ibuprofen rate was 48% higher than the celecoxib rate (incidence rate ratio (IRR) = 1.48; 95% CI = 1.39-1.58; p < 0.001), whereas the naproxen rate was 40% higher (IRR = 1.40; 95% CI = 1.31-1.49; p < 0.001). The association between drug use and UGI symptoms was confirmed by Cox regression analysis; the hazard ratios were 1.21 (95% CI = 1.13-1.29; p < 0.001) for ibuprofen and 1.15 (95% CI = 1.07-1.23; p < 0.001) for naproxen relative to celecoxib. Younger age, female sex, medical history of UGI, cardiovascular and renal conditions, and higher baseline average healthcare expenditures for the 12-month period preceding the index prescription were also significantly associated with an increased incidence of UGI symptoms. CONCLUSIONS: Celecoxib use is associated with a significantly decreased risk of outpatient physician claims for UGI symptoms compared with commonly used prescription nonspecific nonsteroidal anti-inflammatory drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14687808&dopt=Abstract Naproxen Naprosyn