Bioorg Med Chem. 1994 Jul;2(7):715-21.
Enzyme-catalysed enantioselective hydrolysis of racemic naproxen nitrile.

Effenberger F, Bohme J.

Institut fur Organische Chemie der Universitat Stuttgart, Germany.

The bacterial strain Rhodococcus butanica (ATCC 21197), which exhibits nitrilase and nitrile hydratase/amidase activities, catalyses the enantioselective hydrolysis of racemic naproxen nitrile (R/S)-1 to furnish a moderate enantiomeric excess of (S)-naproxen (S)-3. Racemic naproxen amide (R/S)-2 is not a good substrate for this strain. Resting cells of the newly selected bacterial strain Rhodococcus sp. C3II catalyse the enantioselective hydrolyses of racemic naproxen nitrile (R/S)-1 and naproxen amide (R/S)-2 as well, to give (S)-3 in excellent optical (99% e.e.) and good chemical yields in aqueous medium and in the biphasic system of phosphate buffer/hexane.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7858980&dopt=Abstract Naproxen Naprosyn





Drug Metab Dispos. 1987 Nov-Dec;15(6):767-72.
Species-dependent enantioselective glucuronidation of three 2-arylpropionic acids. Naproxen, ibuprofen, and benoxaprofen.

el Mouelhi M, Ruelius HW, Fenselau C, Dulik DM.

Department of Pharmacology & Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.

The enantioselective glucuronidation of several racemic 2-arylproprionic acids (naproxen, ibuprofen, and benoxaprofen) was investigated in vitro with immobilized microsomal protein from human, rhesus monkey, and rabbit liver as the source of UDP-glucuronyl-transferases. Human microsomes, solubilized microsomal protein, and immobilized protein all gave comparable enantioselectivity. The diastereomeric glucuronides were separated and quantitated by HPLC and characterized stereochemically by co-elution with glucuronides formed from authentic resolved enantiomers. Conjugation of the carboxylic acid moieties occurred stereoselectively with all three substrates. However, enantioselectivity varied qualitatively and quantitatively with substrate as well as with species. The glucuronidation of (S)-naproxen by human liver enzymes was inhibited in the presence of (R)-naproxen and vice versa. The ratio of the glucuronides of (S)-benoxaprofen to that of (R)-benoxaprofen in rhesus monkey urine varied between individual animals and appeared to change through time as dosing continued. Hydrolysis of the diasteriomeric glucuronides of (R)- and (S)-naproxen was differentially inhibited by addition of 1,4-saccharolactone.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2893700&dopt=Abstract Naproxen Naprosyn





J Ocul Pharmacol. 1991 Summer;7(2):125-33.
Effects of sodium naproxen eye drops on rabbit ocular inflammation induced by sodium arachidonate.

Spampinato S, Marino A, Bucolo C, Canossa M, Bachetti T, Mangiafico S.

Institute of Pharmacology, University of Bologna, Italy.

Sodium naproxen, a reversible competitive inhibitor of cyclooxygenase, is widely used as an anti-inflammatory agent in clinical practice. The purpose of this study was to determine whether eye drops containing 0.5% (w/v) sodium naproxen reduce a number of inflammatory responses produced by sodium arachidonate in the rabbit's eye. Sodium naproxen eye drops successfully reduced the primary signs of ocular inflammation elicited by 0.5% sodium arachidonate on conjunctiva and iris. However, the drug was less effective in reducing conjunctival inflammation induced by 1% sodium arachidonate. Sodium naproxen treatment significantly reduced the levels of prostaglandin E2 (PGE2), polymorphonuclear leukocytes and protein concentration in aqueous humor samples obtained from the eyes of rabbits treated with 0.5% sodium arachidonate whereas aqueous humor levels of leukotriene B4(LTB4) were not found significantly different from control rabbits. Interestingly, PGE2 as well as LTB 4 "de novo" production by corneas and lenses obtained from rabbits sacrificed 2 h after arachidonate and incubation "in vitro" for 20 min were significantly higher in samples taken from controls than in tissues obtained from the eyes treated with sodium naproxen eye drops. Finally, this drug treatment significantly antagonized the rise in intraocular pressure induced by 0.5% sodium arachidonate. Present data suggest that sodium naproxen may be employed topically to prevent ocular inflammatory reactions where the arachidonic acid cascade is activated.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1655931&dopt=Abstract Naproxen Naprosyn





Gan No Rinsho. 1988 Oct;34(12):1659-62.
[The effect of naproxen on fever following transcatheter arterial embolization of hepatic tumors]

[Article in Japanese]

Miyazaki M, Shimura T, Takahashi O, Kurihara M, Udagawa T, Koshikawa H, Itoh H, Kanno Y, Teramoto O, Kaiho T, et al.

1st Dept. of Surgery, School of Med., Chiba Univ.

In the cases of trans-catheter arterial embolization (TAE) for hepatic malignancies, naproxen has been evaluated for its antipyretic effect. Each patient not given naproxen manifested a remarkable and prolonged fever despite treatment by antibiotics. In those who received an administration of naproxen, however, a significant suppression of fever was achieved (P 0.01-0.001). No remarkable influence was found on the white blood cell counts, the serum GOT and LDH levels by the naproxen. Similarly, no untoward effect due to naproxen was found on the ulcerogenicity in the gastro-duodenum. Thus, for hepatic malignancies, naproxen could be useful in the symptomatic treatment of a fever following a TAE.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3193610&dopt=Abstract Naproxen Naprosyn





Cancer. 1987 Jun 1;59(11):1966-8.
The effect of naproxen on fever in children with malignancies.

Azeemuddin SK, Vega RA, Kim TH, Ragab AH.

Naproxen was used as an antipyretic agent in febrile pediatric cancer patients with evidence of active malignant disease. Sixteen children with leukemia and lymphoma who had fever for more than 72 hours were given naproxen to control fever. Their ages ranged from 16 months to 17 years. There were ten female and six male patients. Their temperature was greater than 38.3 degrees C and the leukocyte count ranged from 400/microliters to 33.3 X 10(3)/microliters, with an absolute neutrophil count (ANC) from 0 to 4514/microliters. The children had no evidence of infection by clinical or laboratory evaluations. All patients were receiving triple antibiotics when naproxen was started. Fourteen patients responded to naproxen with complete lysis of fever within 6 hours of initiation of treatment. Two patients did not respond to naproxen, but proved to have culture-positive infections. There were no side effects from the drug. Naproxen is an effective antipyretic in patients with cancer. It may be useful as a means of differentiating fever secondary to active malignant disease from that due to infection.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3567858&dopt=Abstract Naproxen Naprosyn





Curr Med Res Opin. 1982;8(1):61-6.
A compliance study in general practice of patients switched from phenylbutazone and oxyphenbutazone to naproxen and other non-steroidal anti-inflammatory drugs.

Dickson DJ, English JR.

Fifty-nine patients on long-term treatment with phenylbutazone or oxyphenbutazone for chronic rheumatic conditions were switched to treatment with naproxen and followed-up for 6 months in a compliance study. All patients were started on 500 mg naproxen twice daily but adjustment of the dosage was permitted. During the 6 months of the study only 3 patients returned to treatment with phenylbutazone. Of the remaining 56 patients, 45 were still taking naproxen after 6 months, 9 were changed to other non-steroidal, anti-inflammatory drugs and 2 were lost to follow-up. The study demonstrates that in routine general practice, phenylbutazone and oxyphenbutazone can be successfully replaced by less toxic drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6980773&dopt=Abstract Naproxen Naprosyn





Br J Clin Pharmacol. 1981 Mar;11(3):295-302.
Effect of naproxen on glucose metabolism and tolbutamide kinetics and dynamics in maturity onset diabetics.

Whiting B, Williams RL, Lorenzi M, Varady JC, Robins DS.

1 The influence of the nonsteroidal anti-inflammatory drug naproxen on glucose metabolism and on tolbutamide pharmacokinetics and pharmacodynamics has been studied in ten maturity-onset diabetics. 2 Comparison of both plasma glucose decay curves and insulin responses during an intravenous glucose tolerance test before and after eight 12 hourly doses of naproxen revealed that naproxen had no significant influence on fasting glucose levels or on rates of glucose elimination. 3 When the subjects were given a combination of naproxen and tolbutamide for 3 days naproxen had no influence on tolbutamide absorption, protein binding, disposition or pharmacological effect. 4 Treatment with tolbutamide in maturity-onset diabetics need not be modified if concurrent administration of naproxen is contemplated.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7213531&dopt=Abstract Naproxen Naprosyn