J Chromatogr. 1992 Jun 10;577(2):325-33.
Simultaneous quantitative determination of naproxen, its metabolite 6-O-desmethylnaproxen and their five conjugates in plasma and urine samples by high-performance liquid chromatography on dynamically modified silica.

Andersen JV, Hansen SH.

PharmaBiotec Research Centre, Royal Danish School of Pharmacy, Department of Organic Chemistry, Copenhagen.

The glucuronides of the anti-inflammatory drug naproxen and its metabolite 6-O-desmethylnaproxen have been produced on a preparative scale by enzymatic synthesis. 6-O-Desmethylnaproxen, the glycine conjugate of naproxen and the O-sulphate of 6-O-desmethylnaproxen were prepared by chemical synthesis. Naproxen and the purified metabolite and conjugates were used as standards for the analytical investigation of the metabolic pattern of naproxen in humans. A reversed-phase high-performance liquid chromatographic method based on bare silica dynamically modified with cetyltrimethylammonium ions has been developed. The system was optimized to give a separation of naproxen, 6-O-desmethylnaproxen and five conjugates. Using this method it is also possible to deduce the relationship between the amount of the intact ether-glucuronide and acyl-glucuronide of 6-O-desmethylnaproxen.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1400763&dopt=Abstract Naproxen Naprosyn





Am J Med. 1984 Apr;76(4):597-603.
Utility of naproxen in the differential diagnosis of fever of undetermined origin in patients with cancer.

Chang JC, Gross HM.

The clinical utility of naproxen as an antipyretic agent was examined in the differential diagnosis of fever of undetermined origin in patients with cancer. Twenty-two patients with cancer and fever of undetermined origin for more than seven days were treated with naproxen to control fever when there was no evidence of infection after a careful initial evaluation, and in most cases, after failure of antibiotic therapy. In final analysis, none of five patients with infectious fever had responses to naproxen. In contrast, 14 of 15 patients with neoplastic fever showed a prompt, complete, and sustained lysis of fever within 24 hours after the initiation of naproxen treatment, and the patients also showed symptomatic improvement. One patient with neoplastic fever who did not have a response to naproxen had lysis of fever after the removal of necrotic tumor tissue. Two patients with fever from connective tissue disease had a partial lysis of fever in response to naproxen. These data suggest that naproxen specifically produces the lysis of neoplastic fever and, therefore, is a useful agent in assisting in the differential diagnosis of infectious fever and neoplastic fever in patients with cancer and fever of undetermined origin.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6711574&dopt=Abstract Naproxen Naprosyn





Clin Pharmacol Ther. 1988 Jan;43(1):79-85.
Naproxen kinetics and disease activity in rheumatoid arthritis: a within-patient study.

Van den Ouweland FA, Gribnau FW, Van Ginneken CA, Tan Y, Van de Putte LB.

Department of Medicine, University Hospital St. Radbound, Nijmegen, The Netherlands.

The effects of rheumatoid arthritis disease activity on the pharmacokinetics of the highly albumin-bound nonsteroidal anti-inflammatory drug naproxen were studied in six patients during chronic therapy. In the same patients, kinetics during active disease were compared with those in improvement. Active disease is commonly associated with hypoalbuminemia: 30 +/- 4 gm/L vs. 41 +/- 2 gm/L (mean +/- SD) at the time of improvement. Total naproxen concentrations were significantly lower in active disease, together with a larger apparent volume of distribution (10.6 +/- 1.8 L vs. 8.4 +/- 1.3 L; P less than 0.05) and total body clearance (0.79 +/- 1.8 L/hr vs. 0.59 +/- 0.14 L/hr; P less than 0.001). Peak unbound naproxen concentrations were 29% +/- 19% (P less than 0.05) lower at the time of improvement. The unbound clearance was found diminished during active disease (390 +/- 277 L/hr) in comparison with improvement (488 +/- 343 L/hr; P less than 0.05). Clinical implications of the alterations in naproxen kinetics induced by polyarticular inflammation in patients with rheumatoid arthritis are discussed.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3335121&dopt=Abstract Naproxen Naprosyn





Scand J Rheumatol. 1979;8(1):54-6.
The effect of daily administration of naproxen on the prothrombin complex activity in patients under long-term therapy with phenprocoumon.

Petersen PB, Husted S, Mortensen A, Andreasen F.

Out of a total of 150 patients attending an out-patient clinic for anticoagulant therapy, 12 had disorders which normally would indicate a prolonged use of an antirheumatic drug. To 6 of these patients, naproxen (1/4 g twice daily) was given while anticoagulant treatment with phenprocoumon was continued in an unchanged dosage schedule (average dose 2.1 mg/day). On the average, the prothrombin complex activity (PP%) was reduced to a stable level 10--20% below that obtained during a 2-month period before the naproxen treatment was started. No bleeding episodes or other effects were observed. Thus the simultaneous administration of naproxen caused no problems for the maintenance of a stable anticoagulant therapy.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=311940&dopt=Abstract Naproxen Naprosyn





Biopharm Drug Dispos. 1995 Apr;16(3):201-10.
Pharmacokinetic analysis of diethylcarbonate prodrugs of ibuprofen and naproxen.

Samara E, Avnir D, Ladkani D, Bialer M.

Department of Pharmacy, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel.

The pharmacokinetics of ibuprofen diethylcarbonate (ibudice) and naproxen diethythylcarbonate (napdice), two new diethylcarbonate prodrugs of ibuprofen and naproxen, was investigated in dogs. The rationale for the development of ibudice and napdice was that esterification of the carboxylic moiety of the parent compounds would suppress gastrotoxicity without adversely affecting their anti-inflammatory activity. In addition the biotransformation of the prodrugs to the parent compounds may be utilized to achieve rate and time controlled drug delivery of the active entities. Following oral administration the diethylcarbonate esters were rapidly biotransformed to the parent compounds and no ibudice or napdice was detected in the plasma. The relative bioavailability of ibuprofen and naproxen, following oral administration of ibudice and napdice, was 96% and 74%, respectively, and the rate of absorption was not significantly different from that obtained following oral dosing of the parent compound. Stability studies in gastric and intestinal juice showed that, unlike napdice, ibudice was stable in gastric juice, with both prodrugs undergoing rapid biotransformation to their parent compounds in intestinal juice. This rapid conversion led to the lack of sustained release performance following oral administration of ibudice or napidice.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7787132&dopt=Abstract Naproxen Naprosyn





Eur J Clin Pharmacol. 1991;40(3):209-14.
Response to furosemide during dehydration with and without naproxen pretreatment of kidney donors and renal transplant recipients.

Sjostrom PA, Odlind BG, Hammarlund-Udenaes M.

Department of Internal Medicine, Orebro Medical Centre Hospital, Sweden.

The response to 40 mg furosemide p.o. in 6 healthy kidney donors and 6 renal transplant recipients with and without naproxen pretreatment has been studied. No volume replacement was given in order to study the development of tolerance. The subjects showed an average dehydration of 1.5 kg.6 h-1. While mean creatinine clearance was equal in patients and donors (76 vs 80 ml/min), renal furosemide clearance was significantly lower in the patients (47 vs 81 ml min; P less than 0.05). The patients also excreted a smaller fraction of the dose in the urine (5.7 vs 7.8 mg/6 h; P less than 0.05). As the overall renal sensitivity was similar in the two groups, the natriuretic response was correspondingly smaller in transplant recipients as compared to donors. Within the observation period of 6 h after dosing, acute tolerance developed in the donors and in 4 of the 6 patients, as shown by clockwise hysteresis in the dose (urine furosemide excretion rate)-response (natriuresis) curves. Pretreatment with naproxen reduced renal sensitivity to furosemide (right shift of the dose response curve) in all the donors but in only 2 of the patients. In both groups acute tolerance was less pronounced after naproxen, which may indicate involvement of the prostaglandin system in the development of acute tolerance. The results may also indicate regeneration of sympathetic nerves with functional capacity in at least some renal transplants, or that other mechanisms of salt regulation compensate for loss of sympathetic nerve activity.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2060554&dopt=Abstract Naproxen Naprosyn





Acta Obstet Gynaecol Jpn. 1981 Apr;33(4):449-54.
[Prostaglandins and dysmenorrhea effect of naproxen on prostaglandin concentrations in menstrual blood (author's transl)]

[Article in Japanese]

Ninagawa T, Matsukawa R, Yoshio T, Kan S, Ito K.

It has recently been demonstrated that prostaglandins play an important role in human reproductive system. The purpose of this study is to demonstrate the involvement of PGs in the onset of menstruation and in the cause of dysmenorrhea. In human endometrium PGF2 alpha were found in large amount in late luteal phase and especially in premenstrual period. PGE1 and PGF2 alpha concentrations in menstrual bloods were 3 to 4 times higher in dysmenorrheic subjects as compared to normal women. The high PGE1 and PGF2 alpha concentration of patients decreased to normal level in naproxen treated cycle. And the intensity of abdominal pain and lumbago decreased simultaneously. On the other hand, in normal woman, naproxen gave little effect on PGs concentration of menstrual fluids. High levels of PGs in dysmenorrheic subjects, decrease of PGs concentration by naproxen treatment and simultaneous alleviation of pain suggest the involvement of PGs in the cause of dysmenorrhea.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7234342&dopt=Abstract Naproxen Naprosyn