Clin Pharmacol Ther. 1990 Apr;47(4):540-6.
Coadministration of naproxen and low-dose methotrexate in patients with rheumatoid arthritis.

Stewart CF, Fleming RA, Arkin CR, Evans WE.

Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee-Memphis.

Fifteen patients (30 to 78 years of age) with diagnoses of rheumatoid arthritis were administered oral and intravenous methotrexate (15 mg), alone or with concomitant naproxen (1000 mg/day). Serial blood samples and urine were collected for 24 hours after the dose of methotrexate and were assayed for methotrexate by a specific radioenzymatic method. In twelve patients who completed the study, methotrexate systemic clearance was not statistically different with naproxen (103.3 +/- 35.0 ml/min) versus without naproxen (113.4 +/- 48.3 ml/min; p = 0.37). Oral clearance of methotrexate was not statistically different with naproxen (161.7 +/- 55.0 ml/min) versus without naproxen (176.7 +/- 68.3 ml/min; p = 0.14). Likewise, there was not a significant difference in methotrexate renal clearance or plasma protein binding with or without naproxen. No toxicity was observed when patients received methotrexate alone or with naproxen. This study indicates that concomitant naproxen does not abruptly alter the disposition of low-dose methotrexate in patients with rheumatoid arthritis who have normal renal function.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2328562&dopt=Abstract Naproxen Naprosyn





Pharm Res. 1989 Nov;6(11):919-23.
Macromolecular prodrugs. XV. Colon-targeted delivery--bioavailability of naproxen from orally administered dextran-naproxen ester prodrugs varying in molecular size in the pig.

Harboe E, Larsen C, Johansen M, Olesen HP.

Royal Danish School of Pharmacy, Department of Pharmaceutics, Copenhagen.

The bioavailability of naproxen after oral administration of aqueous solutions of various dextran-naproxen ester prodrugs in pigs was determined. The dextran prodrugs employed ranged in molecular weight from 10,000 to 500,000. As calculated relative to an equivalent oral dose of parent naproxen, the absorption fractions of all the derivatives were close to 100%. Only small interindividual variation of naproxen bioavailability was observed. The naproxen plasma profiles for all the administered prodrugs exhibited a characteristic lag time of naproxen appearance in the blood (2-3 hr). Compared to administration of the prodrugs alone, coadministration of excess of the parent dextran further delayed the absorption of naproxen from the GI tract. The results of the present study demonstrate the potential of dextran prodrugs for colon site-specific delivery of drugs containing a carboxylic acid functional group.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2480587&dopt=Abstract Naproxen Naprosyn





Acta Physiol Hung. 1989;73(1):29-37.
Comparison of the effects on inhibition of cyclooxygenase and thromboxane synthetase on renal excretion and haemodynamics in rats of different ages.

Bartha J, Hably C, Herceg R, Balint G, Braunlich H.

Institute of Physiology, Semmelweis University Medical School, Budapest, Hungary.

Effects of the cyclooxygenase inhibitors indomethacin, naproxen and the thromboxane synthetase inhibitor imidazole on renal sodium water and p-aminohippurate excretion were investigated in sodium loaded conscious rats of different ages. Renal and intrarenal blood flow were studied in anaesthetized adult rats. Indomethacin and naproxen reduced PAH excretion in 5- and 10-day-old rats but not in rats of older ages. Imidazole failed to influence PAH-excretion in young animals. The excretion of PAH was decreased in adult rats at 10 and 60 min following imidazole administration, but not after longer time interval (120 min). Following indomethacin and naproxen administration urine output was decreased in 5-, 10- and 15-day-old rats, but not in rats of older ages. Effects of imidazole on electrolyte excretion can be demonstrated in adult rats only. Cardiac output was not altered by the three drugs. Blood pressure was elevated after indomethacin, but remained unchanged after naproxen and imidazole treatment. Renal and cortical blood flow remained unaltered and no redistribution was seen in intrarenal blood flow after indomethacin, naproxen and imidazole administration. The experimental data suggest that prostaglandins and thromboxanes are involved in the regulation of kidney function, but prostaglandins in the rat--in contrast to the dog--do not seem to play a major role in the regulation of renal vascular tone in adult animals.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2496580&dopt=Abstract Naproxen Naprosyn





Drug Metab Dispos. 1989 Jan-Feb;17(1):43-8.
Isolation and identification of 6-desmethylnaproxen sulfate as a new metabolite of naproxen in human plasma.

Kiang CH, Lee C, Kushinsky S.

Department of Analytical and Metabolic Chemistry, Syntex Research, Palo Alto, CA 94304.

A new metabolite of naproxen, 6-desmethylnaproxen sulfate (6-DMNS), has been identified in plasma from normal and uremic subjects after oral administration of a single 500 mg dose of naproxen. Tentative identification was achieved by the finding of an increase in the concentration of 6-DMN upon incubation of the plasma with arylsulfatase from Helix pomatia or from Aerobacter aerogenes. More definitive identification was established through demonstration that the HPLC retention time of the conjugate is identical to that of an authentic reference sample of 6-DMNS. Unequivocal identification was accomplished by means of LC-MS after the metabolite was isolated from the plasma by protein precipitation with acetonitrile and further purified by anion-exchange and reversed phase HPLC. Plasma profiles of 6-DMNS for normal and uremic subjects, obtained by a procedure involving differential enzymatic hydrolysis using arylsulfatase from H. pomatia, revealed that 6-DMNS was present in plasma from all subjects but in relatively high concentrations only in subjects with impaired renal function and that the extent of the conjugation is related directly to the severity of the dysfunction. No evidence was found for the presence of glucuronide or sulfate conjugates of naproxen in plasma.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2566468&dopt=Abstract Naproxen Naprosyn





Eur J Clin Pharmacol. 1986;31(4):463-8.
Pharmacokinetics of naproxen in elderly patients.

McVerry RM, Lethbridge J, Martin N, Mukerjee SK, Littler T, Tallis R, Sibeon R, Orme ML.

The pharmacokinetics of naproxen have been examined in 13 elderly patients (mean age 84.2 years) and in 9 younger patients (mean age 53.9 years) at the end of a 21 day course of therapy with naproxen 500 mg b.d. The mean pre-dose concentration on days 19, 20 and 21 was significantly higher in the elderly patients than in the controls (60.1 vs. 43.3 micrograms X ml-1). The AUC (0-24) was significantly higher in the elderly subjects only when normalized for body weight (9.1 vs. 5.4 micrograms X ml-1 X h kg-1 p less than or equal to 0.02). The AUC was significantly higher in the elderly group compared to the control group also in the normalized form. The apparent clearance of naproxen was reduced in the elderly compared to the control patients (315 vs. 628 ml X h-1). The percentage protein binding of naproxen was the same in both groups (99.8%) but the free concentration of naproxen was significantly higher in the elderly patients than in the control patients (141 vs. 89.8 ng X ml-1). Although there was no excess of side effects in the elderly patients it is suggested that when naproxen is given to elderly patients, therapy should be started at the lower end of the dosage range.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3643850&dopt=Abstract Naproxen Naprosyn





Br J Clin Pharmacol. 1987 Feb;23(2):189-93.
Naproxen pharmacokinetics in patients with rheumatoid arthritis during active polyarticular inflammation.

van den Ouweland FA, Franssen MJ, van de Putte LB, Tan Y, van Ginneken CA, Gribnau FW.

Patients with rheumatoid arthritis often have hypoalbuminaemia as a sign of disease activity. In view of the extensive binding of naproxen to albumin, the pharmacokinetics of total and unbound drug were studied in eight patients and eight healthy male volunteers during chronic intake of 500 mg twice daily. The area under the serum concentration-time curve of total naproxen during a dose interval, AUC (0,12), smaller in patients (641 +/- 101 mg l-1 h) than in volunteers (896 +/- 85 mg l-1 h; P less than 0.0001). The unbound naproxen AUCu (0,12) was larger in patients (1.9 +/- 0.9 mg l-1 h) than in volunteers (0.7 +/- 0.2 mg l-1 h; P less than 0.01). The higher unbound naproxen concentrations in patients were accompanied by an approximately 40% increase in apparent clearance/bioavailability (CL/F) and a 60% increase in volume of distribution (V/F). Both CL/F and V/F were inversely correlated with the individual serum albumin concentration (r = 0.76, P less than 0.001; r = -0.85, P less than 0.001, respectively). The high unbound naproxen concentration in the serum of patients with active rheumatoid arthritis and concomitant hypoalbuminaemia is not known to be accompanied by an increase in side effects and may be beneficial if anti-inflammatory effects correlate with unbound drug concentration.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3828195&dopt=Abstract Naproxen Naprosyn





J Clin Oncol. 1985 Apr;3(4):552-8.
Neoplastic fever responds to the treatment of an adequate dose of naproxen.

Chang JC, Gross HM.

Twenty-one patients with neoplastic fever due to malignancy were treated with naproxen. A prompt and complete lysis of fever was obtained in 20 patients within 12 hours when an adequate dose of naproxen was given, and a sustained normal temperature was maintained in all responding patients while receiving naproxen except for one in whom a low grade fever recurred. Lysis of fever usually was followed by excessive sweating and subjective symptomatic improvement. However, when naproxen was discontinued in ten patients, febrile state to the pretreatment level recurred in seven patients within three days. This observation suggests naproxen has a definite and effective antipyretic activity against neoplastic fever although it may recur as the drug is discontinued. Naproxen may be a useful adjunctive agent in patients with neoplastic fever for a short-term symptomatic relief.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3981226&dopt=Abstract Naproxen Naprosyn