Int J Clin Pharmacol Ther Toxicol. 1988 Mar;26(3):125-8.
Lack of influence of sulglycotide on naproxen bioavailability in healthy volunteers.

Berte F, Feletti F, di Valserra MB, Nazzari M, Cenedese A, Cornelli U.

Institute of Medical Pharmacology II, University of Pavia, Italy.

We explored the bioavailability and kinetics of naproxen (N) in 12 healthy volunteers treated orally with single doses of 500 mg and retreated after a washout period with the same dose of N plus sulglycotide (S) 200 mg. Naproxen blood levels were measured by high-performance liquid chromatography (HPLC) in samples collected at 0.5, 1, 2, 4, 8, 12, and 24 h of dosing with N or with N + S. No statistically significant difference in terms of naproxen blood levels emerged as the product was administered alone or concurrently with sulglycotide. Peak plasma concentrations and AUC values were 71 +/- 3.16 micrograms/ml and 685 +/- 27 micrograms/ml/h, respectively for N alone, and 72.5 +/- 2.85 micrograms/ml and 651 +/- 28 micrograms/ml/h, respectively for N + S. The difference was not significant. Similarly, the kinetic behavior of naproxen was not modified by the simultaneous presence of sulglycotide, as shown by the t1/2 beta-values obtained with N alone (8.39 +/- 0.31 h) and with N + S (7.93 +/- 0.30 h), and likewise by the distribution volumes at equilibrium (7.63 +/- 0.42 and 7.9 +/- 0.38, respectively), Cmax (63.3 +/- 2.86 and 60.4 +/- 2.9 micrograms/ml, respectively) and tmax (0.95 +/- 0.06 and 1.10 +/- 0.10 h, respectively). From these findings it seems legitimate to claim that sulglycotide can be administered concurrently with naproxen to prevent possible gastric injury by the anti-inflammatory agent thanks to its wellknown antiulcer and cytoprotective activity on the gastric mucosa, without any undue interference with the absorption (hence effectiveness) of naproxen.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3410594&dopt=Abstract Naproxen Naprosyn





Eur J Rheumatol Inflamm. 1983;6(2):216-21.
Double-blind study of suprofen vs naproxen in the treatment of osteoarthritic pain.

Fellmann N, Stocker H, Reuteler H.

In a 2-week double-blind study involving 79 patients with mainly osteoarthritis of the hip and knee, Suprofen and Naproxen were compared for efficacy and tolerability in the treatment of the symptoms of the disease. The drugs were administered on a b.i.d. schedule: 800 mg of Suprofen or 750 mg of Naproxen. Nocturnal pain, pain at rest, pain on motion and tenderness were evaluated at baseline and at days 7 and 14. Results showed that patients in both groups were significantly improved in all parameters. Between the groups no statistically significant differences were found. Thus, Suprofen was as effective in pain relief as Naproxen. One patient in the Suprofen group and two patients in the Naproxen group experienced mild gastrointestinal symptoms. Overall tolerability was very good.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6201367&dopt=Abstract Naproxen Naprosyn





Br J Clin Pharmacol. 1988 Jul;26(1):41-4.
Naproxen kinetics in synovial fluid of patients with osteoarthritis.

Bruno R, Iliadis A, Jullien I, Guego M, Pinhas H, Cunci S, Cano JP.

Recherche Syntex France, Leuville-sur-Orge.

1. The kinetics of naproxen in synovial fluid were studied in 407 osteoarthritic outpatients with knee effusion requiring aspiration, following a single 1100 mg oral dose of naproxen sodium. 2. The drug concentration-time profiles were described by a biexponential function. Naproxen entered synovial fluid rapidly, reaching a maximum concentration of 36 mg l-1 (Cmax) at 7.5 h. The first order input rate constant (kOs) was 0.41 +/- 0.15 h-1 with a lag time (tlag) of 0.24 +/- 0.36 h. 3. Elimination from the fluid was slow (t1/2 = 31 +/- 12 h) and appreciable drug concentrations were still measurable (27 mg l-1) after 24 h. 4. During once daily dosing of naproxen sodium, naproxen should accumulate in synovial fluid, a steady-state being achieved within a week of treatment. The predicted accumulation ratio based on trough concentration was 2.4.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3203059&dopt=Abstract Naproxen Naprosyn





J Pharmacol Exp Ther. 1986 May;237(2):589-99.
Effects of prostaglandin synthesis inhibition on sympathetic-and parasympathetic-mediated coronary hemodynamic responses.

Trimarco B, Cuocolo A, Ricciardelli B, Patrignani P, Volpe M, de Luca N, Condorelli M.

In chloralose-anesthetized dogs with the left circumflex coronary artery perfused at constant flow, the effects of indomethacin or naproxen on coronary and systemic responses to sympathetic and parasympathetic stimulation were evaluated. Sympathetic stimulation was evoked either by 1-min carotid artery occlusion or by epinephrine (5 micrograms) or norepinephrine (5 micrograms) intracoronary administration. Reflex or direct parasympathetic stimulation was produced by ouabain (40 micrograms) or acetylcholine (2.5 micrograms) injection, respectively, in the perfused coronary artery. The administration of indomethacin or naproxen reduced the integrated areas of coronary vasodilatation induced by epinephrine and norepinephrine. The extent of this reduction was dose-dependent with both indomethacin (epinephrine: r = 0.774, n = 35, P less than .001; norepinephrine: r = 0.766, n = 35, P less than .001; norepinephrine: r = 0.799, n = 35, P less than .001) up to 1.5 and 7 mg/kg, respectively. Further increase in dosage of both prostaglandin synthesis inhibitors failed to induce further reduction of integrated areas of coronary vasodilatation. In contrast, the maximum fall in coronary perfusion pressure, induced by both catecholamines, remained unmodified after inhibition of prostaglandin synthesis, whereas a faster return of the perfusion pressure to base line was observed. The extent of cyclooxygenase activity inhibition induced by indomethacin or naproxen, assessed through the radioimmunoassay of thromboxane B2, showed a consistent dose-dependent increase until complete inhibition was attained with 1.5 mg/kg of indomethacin and 7 mg/kg of naproxen. No significant change in the coronary and systemic hemodynamic response induced by carotid occlusion and by ouabain or acetylcholine intracoronary administration was observed. Furthermore, complete cyclooxygenase inhibition, induced by either indomethacin or naproxen, was able to reduce the coronary vasodilatation induced by isoproterenol (5 micrograms) intracoronary injection but failed to modify the coronary vasoconstriction elicited by both epinephrine and norepinephrine in propranolol-treated dogs. These data indicate that the prostaglandin system is involved in the coronary vasodilatation induced by humoral sympathetic stimulation, whereas coronary hemodynamic responses to both neural sympathetic or parasympathetic stimulation are not influenced by the administration of prostaglandin synthesis inhibitors.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3084760&dopt=Abstract Naproxen Naprosyn





Hypertension. 1985 Sep-Oct;7(5):791-6.
Effects of prostaglandin synthesis inhibitors on the renin-angiotensin system and renal function.

Izumi Y, Franco-Saenz R, Mulrow PJ.

Equal doses (8 mg/kg) of the nonsteroidal antiinflammatory drugs indomethacin, naproxen, and sulindac and a large dose of sulindac (32 mg/kg) were administered intragastrically to conscious rats after a normal sodium diet, furosemide stimulation, and a low sodium diet for 8 days. Indomethacin, naproxen, and the high dose sulindac (32 mg/kg) decreased urinary prostaglandin E2 excretion significantly under all experimental conditions. Sulindac (8 mg/kg) suppressed prostaglandin E2 excretion after the normal and low sodium diets but not after furosemide stimulation. Indomethacin decreased plasma active renin levels under all three experimental conditions. In rats receiving a normal sodium diet, indomethacin did not affect free water clearance or renal function; however, after furosemide stimulation or a low sodium diet, indomethacin caused a significant reduction of free water clearance and glomerular filtration rate. Naproxen and sulindac (8 mg/kg) did not suppress active renin under any of the experimental conditions. However, naproxen and sulindac caused a significant reduction in free water clearance and glomerular filtration rate after furosemide stimulation and a low sodium diet. Indomethacin, naproxen, and the high dose sulindac suppressed renal prostaglandin E2 excretion under all experimental conditions. Renal prostaglandin E2 does not appear to be necessary for active renin secretion. Indomethacin is the most potent inhibitor of active renin and, therefore, most likely to cause hyporeninemia. Volume depletion appeared to sensitize the kidney to the adverse effects of nonsteroidal antiinflammatory drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3861577&dopt=Abstract Naproxen Naprosyn





Arzneimittelforschung. 1975 Feb;25(2A):291-2.
[Effect of naproxen on DNA synthesis and DNA repair of human lymphocytes in in vivo experiments]

[Article in German]

Tausch G.

This investigation was conducted in order to evaluate the possibility of late defects caused by drugs. After their base-line blood levels had been assessed, 3 patients with classical rheumatoid arthritis (according to ARA criteria; American Rheumatism Association) received 500 mg of d-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) daily (in capsules). At the peak of naproxen blood levels following the first naproxen dose, and once monthly for 7 months, thereafter, blood samples were drawn. After separating the lymphocytes from the whole blood, they were damaged by means of 60-Co. Hydroxyurea was added for the suppression of their semiconservative DNA-synthesis. The incorporation of 3-H-THYMIDINE INTO THE DNA of the cells was measured after radiation at different incubation periods. The results showed normal behaviour of the DNA-synthesis following naproxen administration in all three patients. The DNA-repair capacity was normal in one female patient, but slightly lowered in the remaining two.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1173776&dopt=Abstract Naproxen Naprosyn





Fertil Steril. 1985 Jun;43(6):922-6.
The effect of naproxen on the concentration of prostaglandins in human seminal fluid.

Bendvold E, Gottlieb C, Svanborg K, Bygdeman M, Eneroth P, Cai QH.

Whole ejaculates were examined for their content of prostaglandins (PGs) during medication with 250 mg naproxen three times daily for 2 weeks. Six volunteers delivered semen samples before, periodically during, and after the period of medication. During treatment with naproxen, the concentration of PGE, PGF, 19-hydroxy-PGE, and 19-hydroxy-PGF significantly decreased. One week after cessation of medication the PG concentration had returned almost to that found before treatment. The four 19-hydroxy-PGF compounds could be determined separately and the relation between them estimated. The proportion of 8 alpha-19-hydroxy-PGF2 alpha increased, whereas that of 8 beta-19-hydroxy-PGF1 alpha decreased significantly during the medication period. No significant influence of the treatment on sperm density or motility could be observed. It is concluded that treatment with naproxen, a potent inhibitor of PG synthesis, significantly reduces the concentration of all PGs present in human seminal fluid. The implication of the effect on human fertility is discussed.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3838947&dopt=Abstract Naproxen Naprosyn