J Reprod Med. 1982 Jul;27(7):423-7.
Naproxen sodium, ibuprofen and a placebo in dysmenorrhea.

Hanson FW.

Seventy-one patients participated, during three dysmenorrheic episodes, in a study that combined a double-blind parallel comparison of naproxen sodium and ibuprofen to each other with a single-blind comparison of naproxen sodium and ibuprofen to a placebo. The comparative measures of efficacy included hourly and overall ratings of pain by patients, limitation of daily activity due to pain and the need for additional pain medication. Although none of these measures showed a statistically significant difference, an analysis of the differences that did emerge showed a trend slightly favoring naproxen sodium. Both drugs were highly effective and significantly superior to the placebo.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6181256&dopt=Abstract Naproxen Naprosyn





Int J Clin Pharmacol Res. 1990;10(5):277-84.
Multiple-dose pharmacokinetics of naproxen from a controlled-release tablet in healthy volunteers.

Palazzini E, Galli G, Babbini M.

Medical Department, Alfa Wassermann S.p.A., Bologna, Italy.

The pharmacokinetics of a new controlled-release tablet of naproxen (750 mg) given once daily has been studied in healthy volunteers, in comparison with two doses of the conventional naproxen tablets (375 and 500 mg) administered twice daily. Steady-state plasma concentrations of naproxen were achieved after two days of repeated administration of both the controlled-release and the conventional tablets. On day seven, peak concentration, cowest concentration and the steady-state average plasma concentration values of the controlled-release tablet were significantly higher than those of 375 mg conventional tablet and comparable to those of 500 mg conventional tablet. Areas under the plasma concentration-time curve indicated an equal extent of absorption between the new and the conventional formulation. Overall the controlled-release tablet administered once daily mimicked a twice daily regimen so suggesting that the new formulation could be suitable for once daily dosing.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2079385&dopt=Abstract Naproxen Naprosyn





Scand J Rheumatol. 1988;17(1):11-6.
Steady state pharmacokinetics of naproxen in elderly rheumatics compared with young volunteers.

Gotzsche PC, Andreasen F, Egsmose C, Lund B.

Rheumatological Department, University Hospital, Hvidovre, Denmark.

The elderly rheumatic patients and 7 healthy young persons received naproxen (Naprosyn, Syntex) 500 mg orally twice a day for 4 weeks. The serum concentrations were determined using mass fragmentography. After an initial 1,000-mg dose, no significant differences were found between the two groups in peak serum concentration, time to peak serum concentration, area below the serum concentration-time curve, volume of distribution, elimination half-life, or total body clearance of naproxen. At steady state, the median total through naproxen concentration was 50.5 mg/l in the elderly and 62.7 in the young (p = 0.08); the unbound concentration was 58 micrograms/l and 44 micrograms/l, respectively (p = 0.06). There was a significant inverse correlation between serum albumin and the free fraction of naproxen (R = -0.58, p = 0.01). The hepatic extraction ratio of naproxen is relatively low and it is suggested that the reduced protein binding in the elderly may conceal the age-related reduction in cellular activity. An estimated value of intrinsic clearance was reduced by 37% in the elderly patients. It is suggested to start naproxen at the lower end of its dose range in the elderly.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3259332&dopt=Abstract Naproxen Naprosyn





J Clin Pharmacol. 1987 Apr;27(4):325-9.
A multiple-dose pharmacokinetic comparison of naproxen as a once-daily controlled-release tablet and a twice-daily conventional tablet.

Ling TL, Yee JP, Cohen A, Hsiao C, Gonzalez MA, Garg DC, Weidler DJ.

Syntex Research, Department of Drug Metabolism, Palo Alto, CA 94304.

The bioequivalence and absorption kinetics of naproxen in a new controlled-release tablet (750 mg or 1,000 mg naproxen) administered once daily were determined relative to an equivalent dose of the conventional naproxen tablet (375 mg or 500 mg naproxen) administered q12h. Naproxen was well absorbed from the controlled-release tablet (about 90%) compared with the conventional tablet. Absorption was dependent on drug release from the tablet matrix. The mean absorption time of naproxen averaged 8.4 hours for the 750-mg controlled-release tablet and 9.2 hours for the 1,000-mg controlled-release tablet. Once-daily administration of the controlled-release tablet resulted in equivalent trough concentrations of naproxen, and steady-state plasma concentrations were maintained within narrower limits than with twice-daily naproxen.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3680592&dopt=Abstract Naproxen Naprosyn





Arzneimittelforschung. 1993 Jun;43(6):675-9.
Pharmacokinetics and pharmacodynamics of naproxen in acute experimental hepatitis.

Favari L, Castaneda-Hernandez G, Hoyo-Vadillo C.

Departamento de Farmacologia y Toxicologia, Centro de Investigacion, Mexico City, Mexico.

The pharmacokinetics of intravenous naproxen (CAS 22204-53-1) 6 mg kg-1, were studied in Wistar rats under control conditions and 1, 3 and 10 days after the induction of acute hepatitis by a single intraperitoneal injection of galactosamine 375 mg kg-1. In non-intoxicated rats t1/2 was 5.31 +/- 0.90 h, Vd was 0.21 +/- 0.01 l.kg-1, Cl was 17 +/- 5 ml.h-1.kg-1, AUC was 354.4 +/- 8.8 micrograms.h.ml-1 and 99.18 +/- 0.09% of naproxen was bound to plasma proteins. One day after intoxication the liver was considerably damaged; cytochrome P450, the main enzymatic system for naproxen metabolism, was decreased in 90%. Naproxen t1/2 was increased to 11.9 +/- 1.2 h but Vd did not change significantly, therefore clearance was reduced to 37%. Binding to plasma proteins was decreased to 83.21 +/- 0.27%. At day 3 liver function and naproxen pharmacokinetics exhibited a partial recovery, t1/2 was 6.59 +/- 0.92 h and clearance was 12.2 +/- 5 ml.h-1.kg-1 being not significantly different from controls; notwithstanding AUC was still significantly different from that of non-intoxicated rats. 10 days after galactosamine injection all pharmacokinetic parameters, as well as those of liver function, returned to basal levels. The results indicate that acute hepatitis produces an important reduction in naproxen elimination. Changes in naproxen disposition, which exhibit a time course similar to that of liver damage, are mainly determined by a decrease in intrinsic hepatic clearance and in the binding to plasma proteins.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8352821&dopt=Abstract Naproxen Naprosyn





Exp Gerontol. 1995 Sep-Oct;30(5):505-15.
Effects of age on the pharmacodynamics of naproxen in the rat.

Satterwhite JH, Boudinot FD.

Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens 30602-2353, USA.

The pharmacodynamics of naproxen were evaluated in 5- and 24-month-old male Fischer 344 rats. Plasma naproxen concentrations and thromboxane B2 (TxB2) concentrations were measured as a function of time after intravenous administration of 25 mg/kg naproxen. Age-dependent alterations in naproxen pharmacokinetics were attributed to significant reductions in free plasma clearance (CLfree) and free steady-state volume of distribution (VSSfree), suggesting a decline in metabolic activity and naproxen binding to tissue components in aged rats, respectively. The time course of TxB2 production as a function of unbound naproxen concentrations was described by a sigmoid Emax model. Age had no significant effect on the pharmacodynamic parameter Emax, the maximum percent inhibition of TxB2 formation. Age also had no statistically significant effect on EC50, the drug concentration producing 50% of the maximum effect, however, average EC50 values were 35% higher in the aged rats. The duration of TxB2 inhibition was unaffected by age, possibly owing to similar relative decreases in receptor sensitivity (increased EC50) and increases in free naproxen concentrations (decreased free clearance and volume of distribution). Alternatively, the age-related changes in pharmacokinetic parameters were not of sufficient magnitude to produce a significant change in drug response, naproxen, pharmacokinetics, pharmacodynamics, age, rats, thromboxane B2, nonsteroidal anti-inflammatory drugs.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8557098&dopt=Abstract Naproxen Naprosyn





J Chromatogr. 1990 Sep 28;518(1):157-65.
Sensitive analysis of phospholipid molecular species by high-performance liquid chromatography using fluorescent naproxen derivatives of diacylglycerols.

Rastegar A, Pelletier A, Duportail G, Freysz L, Leray C.

Centre de Neurochimie du CNRS, Strasbourg, France.

A sensitive high-performance liquid chromatographic (HPLC) method for the separation and determination of diacylglycerophospholipid and diacylglycerol (DAG) molecular species has been developed. Phospholipids are hydrolysed with phospholipase C and the resulting DAGs are reacted with naproxen chloride in the presence of 4-dimethylaminopyridine. The naproxen-DAGs were purified by thin-layer chromatography on silica gel G plates. Molecular species were separated using reversed-phase HPLC with isocratic elution and determined by measuring the absorbance at 230 nm or fluorescence at 352 nm (excitation at 332 nm). The method was applied to the determination of diacylglycerophosphoethanolamine in rat cerebrum and cerebellum. The molar absorption coefficient of the naproxen derivatives was 53,000 lmol-1 cm-1 at 230 nm, permitting the generation of linear concentration-dependent determinations down to less than 10 pmol. A ten-fold increase in sensitivity was obtained with a fluorescence detection system owing to the fluorescent properties of the proposed adduct.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2258403&dopt=Abstract Naproxen Naprosyn