Biopharm Drug Dispos. 1993 Aug;14(6):491-502.
Pharmacokinetics of naproxen, its metabolite O-desmethylnaproxen, and their acyl glucuronides in humans.

Vree TB, van den Biggelaar-Martea M, Verwey-van Wissen CP, Vree JB, Guelen PJ.

Department of Clinical Pharmacy, Academic Hospital Sint Radboud, Nijmegen, The Netherlands.

The aim of this investigation was to assess the pharmacokinetics of naproxen in 10 human subjects after an oral dose of 500 mg using a direct HPLC analysis of the acyl glucuronide conjugates of naproxen and its metabolite O-desmethylnaproxen. The mean t1/2 of naproxen in 9 subjects was 24.7 +/- 6.4 h (range 16 to 36 h). The t1/2 of 7.4 as found in subject number 10 must, therefore, be regarded as an extraordinary case (p < 0.0153). Naproxen acyl glucuronide accounts for 50.8 +/- 7.32 per cent of the dose, its isomerized conjugate isoglucuronide for 6.5 +/- 2.0 per cent, O-desmethylnaproxen acyl glucuronide for 14.3 +/- 3.4 per cent, and its isoglucuronide for 5.5 +/- 1.3 per cent (n = 10; 100 h collection period). Naproxen and O-desmethylnaproxen are excreted in negligible amounts (< 1 per cent). Even though urine pH of the subjects was kept acid (range pH 5.0-5.5) in order to stabilize the acyl glucuronides, isomerization takes place in blood when the acyl glucuronide is released from the liver for excretion by the kidney. Binding to plasma proteins was measured as 98 per cent and 100 per cent, respectively for the unconjugated compounds naproxen and O-desmethylnaproxen. Binding of the acyl glucuronides was less, being 92 per cent; for naproxen acyl glucuronide, 66 per cent for naproxen isoglucuronide, 72 per cent for O-desmethylnaproxen acyl glucuronide and 42 per cent for O-desmethylnaproxen isoglucuronide.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8218967&dopt=Abstract Naproxen Naprosyn





Pharmacol Res. 1995 Jan;31(1):61-5.
Anti-inflammatory potency and gastrointestinal toxicity of a new compound, nitronaproxen.

Cuzzolin L, Conforti A, Adami A, Lussignoli S, Menestrina F, Del Soldato P, Benoni G.

Institute of Pharmacology, University of Verona, Italy.

Naproxen and its derivative nitronaproxen at the doses of 5 and 10 mg kg-1 were compared for their acute anti-inflammatory efficacy in a carrageenan oedema model and gastrointestinal toxicity in rats. Moreover, the effects of the two drugs were evaluated in the adjuvant arthritis, after chronic doses of 4 and 8 mg kg-1 administered orally for 18 days. The oedema reduction was maintained much longer (until 5 h) with nitronaproxen; the inhibition of arthritis was 50% or more with both doses of the examined drugs. From the histological examination of the stomachs, an extensive mucosal vasocongestion and haemorrhagic lesions have been observed in some rats treated with naproxen. The percentages of animals with ulcers were 50, 100 and 10 with naproxen 6 and 18 mg kg-1 and nitronaproxen 54 mg kg-1 respectively. A better gastrointestinal tolerability has been observed in arthritic and oedemic rats treated with nitronaproxen compared to naproxen: this could be due to the presence of nitric oxide that acts in maintaining the tissue perfusion and integrity.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7784307&dopt=Abstract Naproxen Naprosyn





Gan No Rinsho. 1987 Sep;33(11):1347-52.
[Antipyretic effect of naproxen in neoplastic fever]

[Article in Japanese]

Kondo M, Ando Y, Tominaga S, Nakayama T, Kuribayashi T, Hashimoto S.

Dept. of Radiology, Keio Univ. School of Med.

Naproxen has been administered for 22 febrile episodes of unknown etiology in 21 patients with malignant tumors. Ten patients had malignant lymphomas, and the others had solid tumors. The highest temperature was 38.5 degrees C or more in all but one of the patients. Out of the 22 episodes, 2 episodes were found to have been caused by an infection. The naproxen doses ranged from 300 to 600 mg per day. Of the 20 episodes of neoplastic fever, the temperature decreased 1.0 degree C or more in 16 patients, in 13 of whom the temperature decreased to 37.0 degrees C or less. There was some evidence that suggests the existence of a dose-response relation-ship. The initial use of 600 mg per day seemed to be appropriate. The antipyretic effect did not seem to be influenced by the type of the underlying tumors. Three patients continued to receive naproxen for one to to months. No side effect was observed, excepting for one patient who developed a mild nausea. We thus conclude that naproxen is an effective safe drug for the control of neoplastic fever.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3669320&dopt=Abstract Naproxen Naprosyn





J Pharm Sci. 1979 Jan;68(1):112-4.
Enantiomeric purity of naproxen by liquid chromatographic analysis of its diastereomeric octyl esters.

Johnson DM, Reuter A, Collins JM, Thompson GF.

A sensitive and specific analytical method was developed to determine the enantiomeric purity of naproxen. A simple derivatization of naproxen with (S)-(+)-2-octanol proceeded quantitatively and gave a mixture of diastereomeric esters displaying baseline separation on liquid chromatography. The ratio of these esters was the same as the ratio of enantiomers present in naproxen samples assayed. Reproducibility of the method was excellent.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=758445&dopt=Abstract Naproxen Naprosyn





J Rheumatol. 1993 Oct;20(10):1764-8.
Pilot investigation of naproxen/methotrexate interaction in patients with juvenile rheumatoid arthritis.

Wallace CA, Smith AL, Sherry DD.

Department of Pediatrics, University of Washington, Seattle.

OBJECTIVE: To investigate the potential interaction of naproxen and methotrexate (MTX) in children with juvenile rheumatoid arthritis (JRA). METHODS. Nine children with JRA served as their own control taking their usual doses of MTX (0.22-1.02 mg/kg/week) and naproxen (14.6-18.8 mg/kg/day) separately and in combination. RESULTS. MTX affected a > or = 30% change in naproxen kinetics in 6/8 patients, while naproxen altered MTX kinetics by > or = 30% in 4/9 patients. CONCLUSION. MTX can alter nonsteroidal antiinflammatory drug (NSAID) kinetics in children with JRA and NSAID can alter MTX kinetics. NSAID toxicity should be considered when assessing adverse reactions in patients receiving the combination treatment of MTX and NSAID.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8295192&dopt=Abstract Naproxen Naprosyn





Acta Pharmacol Toxicol (Copenh). 1981 Nov;49(5):327-33.
Effects of indomethacin, naproxen and paracetamol on regional blood flow in rabbits: a microsphere study.

Hierton C.

Ulcerogenic side-effects and prostaglandin-synthesis-inhibiting capacity are well documented in indomethacin treatment. According to recent works, indomethacin reduces gastrointestinal blood-flow. Naproxen and paracetamol, claimed to be prostaglandin-synthesis-inhibitors, have few ulcerogenic side effects. In an attempt further to study the indomethacin effects and to reveal whether naproxen and paracetamol have similar effects, the labelled microsphere technique was used. The regional blood flow determinations were made before, and 12-15 min. after, the injection of the drugs. Indomethacin 3 mg/kg, reduced gastrointestinal blood flow and increased arterial blood flow to the liver. Naproxen, 10 mg/kg, and paracetamol, 25 mg/kg, had no effects except for a very small decrease in liver blood flow with paracetamol. The results strongly suggest that, at least under light general anaesthesia, prostaglandins influence resting blood flow in the gastrointestinal tract, the liver and parts of the brain. The results more raise doubts whether naproxen and paracetamol inhibit prostaglandin synthesis in these tissues. These data offer a plausible explanation as to why naproxen and paracetamol are usually well tolerated in the gastrointestinal tract. None of the drugs tested influenced resting blood flow in muscles, tendons, bones, joints or synovial membranes.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7345878&dopt=Abstract Naproxen Naprosyn





Circulation. 1985 Apr;71(4):840-8.
Late phase of nitroglycerin-induced coronary vasodilatation blunted by inhibition of prostaglandin synthesis.

Trimarco B, Cuocolo A, Van Dorne D, Ricciardelli B, Volpe M, De Simone A, Condorelli M.

In chloralose-anesthetized dogs with the left circumflex coronary artery perfused at constant flow, the effects of increasing doses of indomethacin or naproxen on the coronary and systemic hemodynamic responses to a 5 microgram intracoronary injection of nitroglycerin (NTG) were evaluated. The integrated areas of NTG-induced coronary vasodilatation were reduced after administration of indomethacin or naproxen. The extent of this reduction was increased progressively by augmenting the dose of indomethacin and naproxen up to 1.5 and 7 mg/kg, respectively. We also assessed the extent of cyclooxygenase inhibition induced by indomethacin or naproxen through the radioimmunoassay of thromboxane B2, which reflects thrombin-induced activation of platelet thromboxane A2 production during whole blood clotting. The level of inhibition progressively increased and complete inhibition was attained with 1.5 mg/kg indomethacin and 7 mg/kg naproxen. Further increase in dosage failed to induce further reduction of integrated areas of coronary vasodilatation, and a correlation was found between the extent of the reduction of the integrated areas of coronary vasodilatation and the dose of indomethacin (r = .828, n = 35, p less than .001) or naproxen (r = .729, n = 35, p less than .001). Finally, the NTG-induced maximum fall in coronary perfusion pressure remained unmodified after inhibition of prostaglandin synthesis, but there was a faster return of the perfusion pressure to the basal value.(ABSTRACT TRUNCATED AT 250 WORDS)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3918808&dopt=Abstract Naproxen Naprosyn