Jpn J Physiol. 1996 Feb;46(1):67-73.
Hematologic and body fluid changes during simulated high altitude exposure in naproxen-treated rats.

Biswas HM, Saha RC, Biswas NM.

Department of Physiology, University College of Science and Technology, Calcutta, India.

Arterial blood oxygen saturation, body fluid and hematological parameters were studied in control, naproxen (a prostaglandin synthesis inhibitor)-treated control, altitude-exposed, and naproxen-treated altitude-exposed rats after intermittent exposure of 8 h/d for 6 consecutive days to a simulated high altitude of 6,100 m (barometric pressure 349 +/- 3 mmHg). Arterial blood oxygen saturation was reduced in altitude-exposed rats, but increased significantly to near control level in naproxen-treated rats. On the other hand, 2,3-diphosphoglycerate in erythrocytes increased in altitude-exposed rats, but naproxen prevented this increase. The red blood cell count, hemoglobin concentration and hematocrit ratio were reduced significantly in drug-treated altitude-exposed rats when compared to the altitude-exposed group (without drug). Red cell mass was increased in the altitude-exposed group in comparison with control. Both red cell mass and mean corpuscular volume of altitude-exposed rats were shifted towards the control value when they were treated with naproxen. Drug-treated high altitude-exposure reduced the thiocyanate space, intracellular fluid volume and total body water content compared to drug-treated control rats. On the other hand, thiocyanate space and total body water content were increased significantly in drug-treated control rats in comparison with the control group.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8743720&dopt=Abstract Naproxen Naprosyn





J Chromatogr. 1992 Jul 24;578(2):251-7.
High-performance liquid chromatographic determination of naproxen, ibuprofen and diclofenac in plasma and synovial fluid in man.

Blagbrough IS, Daykin MM, Doherty M, Pattrick M, Shaw PN.

Department of Pharmaceutical Sciences, University of Nottingham, University Park, UK.

High-performance liquid chromatographic assay procedures have been developed for naproxen, ibuprofen and diclofenac in human plasma and synovial fluid samples. A single liquid-liquid extraction procedure was used to isolate each compound from acidified biological matrix prior to the quantitative analysis. A Spherisorb ODS column (12.5 cm x 4.6 mm I.D.) was used for all the chromatography. Naproxen was eluted with a mobile phase of methanol-Sorensen's buffer at pH 7 (37:63, v/v). Ibuprofen and diclofenac were eluted using mobile phases of methanol-water at pH 3.3 (65:35, v/v and 63:37, v/v, respectively). Diphenylacetic acid was used as the internal standard for the assay of naproxen and flurbiprofen was used in the analysis of ibuprofen and diclofenac. Inter- and intra-day coefficients of variation were less than 7%. The assays were used in clinical studies of the three drugs in osteo- and rheumatoid arthritis patients.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1400804&dopt=Abstract Naproxen Naprosyn





Fundam Clin Pharmacol. 1991;5(4):275-83.
Determination of free concentration of piroxicam and naproxen in plasma. The influence of experimental conditions in equilibrium dialysis.

Hundal O, Rugstad HE.

Dept of Clinical Pharmacology, National Hospital, Oslo, Norway.

An equilibrium dialysis method was established in order to investigate possible relationships between free drug concentrations of piroxicam and naproxen and clinical events. Therefore the influence of variations in pH, phosphate concentration and sodium azide concentration of the dialysis buffer on the free concentrations of piroxicam and naproxen was investigated. Piroxicam was found to have a pH-dependent protein binding. Therefore a good control of pH during the dialysis process is necessary. This has been achieved by increasing the buffer capacity of the dialysis buffer, by adding an antibacterial agent to the dialysis buffer and by cleansing the dialysis cells with 70% ethanol before use to prevent bacterial growth. Addition of 0.03% sodium azide as an antibacterial agent and the use of a 0.09 mol/l phosphate buffer gave good pH control. A method to correct for deviations of pH in measurements of free concentrations of piroxicam by a simple mathematical correction has been found. As naproxen was found to have a protein binding independent of pH, a pH-correction is not necessary for this drug. Standardized conditions in determination of protein binding of drugs by equilibrium dialysis are important, as composition of the dialysis buffer and pH of plasma compartment at equilibrium may influence the free concentration measurements. Comparisons of data from experiments using different methods are therefore difficult; the importance of pH-control is stressed. With the methods used in the present investigation, equilibrium dialysis in connection with HPLC, the coefficients of variation for piroxicam and naproxen free concentrations are 5.5% and 7.4%, respectively.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1916611&dopt=Abstract Naproxen Naprosyn





Eur J Clin Pharmacol. 1994;46(1):3-7.
Sodium naproxen: concentration and effect on inflammatory response mediators in human rheumatoid synovial fluid.

Bertin P, Lapicque F, Payan E, Rigaud M, Bailleul F, Jaeger S, Treves R, Netter P.

Clinique Therapeutique et Rhumatologique, Hopital Universitaire Dupuytren, Limoges, France.

Twelve patients suffering from rheumatoid arthritis and having swollen knees were treated with 1.1 g/day of sodium naproxen administered in one dose, daily for 5 days. The 72-h wash-out period was verified by the absence of any nonsteroidal anti-inflammatory drug using a HPLC screening. Blood and synovial fluid samples were drawn just before treatment and 24 h after the last dose. Eicosanoids (PGE2, 6-keto-PGF1 alpha, TXB2, LTB4, LTC4) in synovial fluid were determined by immunoenzymatic assays. In plasma and synovial fluid, hyaluronic acid was assayed by radiometric assay and sodium naproxen by HPLC. Free drug was determined by equilibrium dialysis. Statistical analysis used nonparametric tests. Pain relief (evaluated on a visual scale), morning stiffness, and scores on the Lee and Ritchie indices all decreased significantly, as did PGE2 and LTB4 concentrations. The decrease in 6-keto-PGF1 alpha and TXB2 was not significant. No significant change was found for LTC4 and hyaluronic acid. Total concentrations of sodium naproxen were equivalent in plasma (16.1 micrograms.ml-1) and synovial fluid (18.9 micrograms.ml-1). Free fractions were significantly higher in synovial fluid (0.14%) than in plasma (0.11%), as shown by binding of the drug to human serum albumin, at various protein concentrations. Interestingly, the clinical efficacy, as shown by decreases in morning stiffness and in the Lee index score, correlated with the free concentration of naproxen in synovial fluid.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8005184&dopt=Abstract Naproxen Naprosyn





Arthritis Rheum. 1979 Dec;22(12):1365-74.
Effects of naproxen on connective tissue changes in the adjuvant arthritic rat.

Ackerman NR, Rooks WH 2nd, Shott L, Genant H, Maloney P, West E.

The Freund's adjuvant-injected rat shares a number of features with the arthritis patient, viz the presence of a proliferative synovitis, joint swelling, and cartilage and bone erosion. Naproxen, a prostaglandin synthetase inhibitor which is an effective antiinflammatory agent in laboratory animals and humans, was evaluated as an inhibitor of connective tissue destruction in this model by use of radiologic and histopathologic analyses. Sixteen days after rats were injected with Freund's complete adjuvant, marked joint swelling was noted. On day 17, vehicle or naproxen, 7 mg/kg/day, was administered orally. Twenty-eight days later vehicle-treated animals demonstrated the following pathologic changes in their hindpaws; swelling, cartilage loss, large amounts of pannus within the joint spaces, osteoporosis, bone erosions, periosteal new bone formation, heterotopic ossification, and bony ankylosis. Rats treated 28 days with naproxen had significantly milder disease than the vehicle controls. The incidence of severe juxtaarticular bone destruction was 10/10 in the vehicle controls versus 2/10 of the drug-treated group (P less than 0.01). A comparable reduction in cartilage erosion, incidence of pannus, and new bone formation was noted in the drug-treated group. These effects may relate to an inhibition of prostaglandin biosynthesis; prostaglandins have been shown to: 1) stimulate collagenase secretion from macrophages, 2) stimulate bone resorption in vivo and in vitro, and 3) diminish proteoglycan synthesis in cartilage.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=518718&dopt=Abstract Naproxen Naprosyn





Int J Clin Pharmacol Ther Toxicol. 1991 Jul;29(7):253-6.
Pharmacokinetics of a controlled release preparation of naproxen.

Strocchi E, Ambrosioni E, Palazzini E, Galli G.

Cattedra di Terapia Medica Sistematica, Universita di Bologna, Italy.

The pharmacokinetics of a controlled release preparation of naproxen (750 mg) was compared with that of standard release naproxen, in 12 healthy volunteers. The plasma levels of naproxen and urinary recoveries of naproxen and metabolites were determined both after single doses and chronic administration. The experimental data show that the bioavailability of the controlled release preparation is equal to that of standard release naproxen; however, the controlled release preparation allows more constant plasma levels of naproxen and, when administered once a day for prolonged periods, is capable of maintaining effective concentrations for most of the dosing period.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1889910&dopt=Abstract Naproxen Naprosyn





Yao Xue Xue Bao. 1989;24(4):280-4.
[Spectrophotometric determination of complex formation constants of naproxen with caffeine, nicotinamide and salicylic acid in aqueous solution]

[Article in Chinese]

Shi QH, Wang JJ, Liu XD, Zhang JH.

The interaction between water insoluble drug naproxen with caffeine, nicotinamide and salicylic acid in aqueous solutions were determined by spectrophotometry. Naproxen was found to form 1:1 molecular complex with these substances. The complex formation constants were determined by spectrophotometry at room temperature. The thermodynamic functions associated with complexation of naproxen-drugs were also evaluated. It may be concluded that the complex formation may be attributed to hydrogen bonding since enthalpy changes were shown to be a few KJ.mol-1.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2530752&dopt=Abstract Naproxen Naprosyn