Methods Find Exp Clin Pharmacol. 1983 Nov;5(9):625-9.
Quantitative study on the uterus-inhibiting activity of sodium naproxen in rat isolated uterus.

Perez-Baspino J, Vaca-Vaca JM, Corbalan AJ, Brugger AJ.

Action of Sodium Naproxen on spontaneous and field stimulated motility of isolated rat uterus was studied. Sodium Naproxen inhibited both spontaneous and field stimulated motility. The IC50 on spontaneous motility was lower than the IC50 on stimulated motility. The inhibition produced on the field stimulated uterus was more regular in relationship to concentration used of Sodium Naproxen. The IC50 of Sodium Naproxen in these experimental conditions was 8.22 X 10(-4) M (pD2 = 3.09 +/- 0.02) and the maximum inhibitory effect was 100%. These results show that prostaglandin synthesis plays a necessary role in uterine contraction, spontaneous or induced by field stimulus.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6668972&dopt=Abstract Naproxen Naprosyn





Prostaglandins Med. 1979 Apr;2(4):299-315.
Effects of naproxen on uterine contractility in vivo.

Vickery BH.

An in vivo technique for monitoring uterine contractility has been developed and used to assess the effects of naproxen on both spontaneous motility and that due to exogenous PGF2 alpha in the hamster and the rat. Naproxen has been shown to suppress uterine motility in both situations, in both species, whether administered by parenteral or oral routes. The hamster was shown to be approximately 10 X less sensitive to naproxen than is the rat (625 mg/kg vs 62.5 mg/kg) but conversely was 100 X more sensitive than rat to uterine contractive effects of PGF 2 alpha (10 ng vs 1000 ng).

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=550148&dopt=Abstract Naproxen Naprosyn





Eicosanoids. 1989;2(1):47-9.
Influence of naproxen on uterine PGF2 alpha and the antifertility effect of IUDs in rats.

Tang DC, Wu XR, Zhao BR, Liu YQ, Li Y.

Family Planning Research Institute, Tongji Medical University, Wuhan, People's Republic of China.

An IUD was implanted into one horn of the uterus in each of our experimental rats. The animals were mated with males of proven fertility about 2 weeks later. At day 1 of gestation (positive mating smear), the animals were treated with oral naproxen at 2 mg/kg per day or 20 mg/kg per day for 10 consecutive days. Control animals received saline. At day 16 the animals were sacrificed and the implantation rates and fetal survival and pregnancy rates were determined. The IUD completely prevented fetal survival and largely reduced implantation rates. Naproxen did not modify these parameters in either the IUD or the non-IUD horn. In a separate set of experiments, the reduction in uterine levels of immunoreactive PGF2 alpha (iPGF) was measured during the implantation period. Naproxen treatment for 5 days with 2 mg/kg per day or 20 mg/kg per day reduced iPGF from 6.71 +/- 0.93 to 2.19 +/- 0.34 and 1.01 +/- 0.18 ng/100 mg tissue, respectively (P less than 0.01). These data show that the suppression of uterine PG synthesis by naproxen does not interfere with the antifertility effects of IUDs in the rat.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2633796&dopt=Abstract Naproxen Naprosyn





Eur J Drug Metab Pharmacokinet. 1988 Oct-Dec;13(4):267-71.
Coupling of TLC and UV-measurement for quantification of naproxen and its main metabolite in urine.

Abdel-Moety EM, Al-Obaid AM, Jado AI, Lotfi EA.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

A simple sensitive method of high specificity and selectivity for quantitative determination of the non-steroidal anti-inflammatory drug naproxen and its main metabolite, 6-demethylated derivative, in biological specimens is described. Like naproxen, its metabolite absorbs maximally at 232 nm; this makes their simultaneous quantification, via direct UV-measurements at lambda max, in biological fluids quite impossible. Simple TLC-separation on silica gel F254 using chloroform + methanol (85:15, v/v) achieved the best fractionation of the unchanged drug and its metabolite from the matrix-contents of urine. UV-quantification of fractionated components could reach concentration levels of 0.2-3.0 micrograms ml-1 (ppm) in worked up urine samples. Varying levels of unchanged antiinflammatory drug and the phenolic metabolite could be accurately traced in urine samples following a 2.9 mg/kg oral dose after different time-intervals. Synthetic preparation of the metabolite by demethylation of naproxen is briefly mentioned.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3243322&dopt=Abstract Naproxen Naprosyn





J Clin Pharmacol. 1976 Apr;16(4):189-93.
Naproxen plasma levels in volunteers after single-dose administration by oral and rectal routes.

Desager JP, Vanderbist M, Harvengt C.

The bioavailability (plasma concentrations, AUC) of a rectal formulation (suppository) of naproxen was investigated in six healthy volunteers by comparison with an oral preparation (tablets). Plasma half-lives after both formulations were identical 10 hr 15 min+/-25 min (S.D.). Determined by the AUC the bioavailability of naproxen in the suppositories was 94.8%+/-6.3% of the bioavailability of naproxen in the tablets. This paper describes also a new gas-liquid chromatographic method for determining unchanged naproxen in human plasma which is quick, sensitive, and specific.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1262531&dopt=Abstract Naproxen Naprosyn





Clin Pharmacol Ther. 1977 Nov;22(5 Pt 1):545-9.
Plasma protein binding of basic drugs. II. Importance of alpha 1-acid glycoprotein for interindividual variation.

Piafsky KM, Borga O.

The protein binding of two basic drugs, alprenolol and imipramine, and the acidic drug, naproxen, was determined in plasma obtained from 23 healthy subjects. A 2-fold variation was found between individuals in the free fraction of the two bases, while the range was even greater with naproxen. The free fraction correlated with the plasma concentration of alpha 1-acid glycoprotein for alprenolol (r = -0.75, p less than 0.001) and imipramine (r = -0.78, p less than 0.001), while there was no correlation for naproxen (r - 0.24, p greater than 0.1). This confirms recent experiments which showed that isolated alpha 1-acid glycoprotein avidly bound both alprenolol and imipramine. Drug binding, however, did not correlate with albumin concentration, although experiments with isolated albumin demonstrated its unusually high affinity for naproxen.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=913021&dopt=Abstract Naproxen Naprosyn





Agents Actions. 1992 Sep;37(1-2):90-8.
Antiarthritic profile of BF-389--a novel anti-inflammatory agent with low ulcerogenic liability.

Wong S, Lee SJ, Frierson MR 3rd, Proch J, Miskowski TA, Rigby BS, Schmolka SJ, Naismith RW, Kreutzer DC, Lindquist R.

Biofor Limited, Waverly, PA.

BF-389, dihydro-4-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-methyl-2H-1,2- oxazin-3(4H)-one, is a potent, orally active, antiarthritic and analgesic agent with low ulcerogenic potential. A comparison of the activity profiles of BF-389 and naproxen showed similarities in: (1) suppression of developing and chronic adjuvant arthritis (AA); (2) maximal inhibitory response, as shown by the E(max) values in the developing and established AA models; (3) inhibition of bone degenerative changes associated with chronic adjuvant arthritis; and (4) analgesic activity in the acetic acid and phenylquinone writhing assays. Though BF-389 has been shown to be a potent inhibitor of cyclooxygenase, IC50 = 0.84 +/- 0.25 microM against the production of PGE2 in vitro, there is a great difference from most cyclooxygenase inhibitors; it also inhibits the 5-lipoxygenase enzyme. For BF-389, the IC50 for in vitro LTB4 formation was found to be 3.65 +/- 1.19 microM. The ulcerogenic potential of BF-389 was compared to that of naproxen using a five-day in vivo ulcerogenic rat assay. The UD50 for naproxen was found to be approximately 30 mg/kg/day, p.o. Based upon efficacy in the DEV AA and EST AA models, UD50/ED50 values for naproxen were estimated to be 0.7 and 1.9, respectively. For BF-389 the UD50 was shown to be 520 (389-695) mg/kg/day, p.o., and the corresponding UD50/ED50 values were calculated to be 84 and 28, respectively, thus demonstrating the wide margin of safety between efficacy and ulcerogenicity in rats.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1456184&dopt=Abstract Naproxen Naprosyn