Prostaglandins Med. 1979 May;2(5):325-35.
Prolongation of gestation in the rat and hamster by naproxen.

Vickery B.

Administration of naproxen by once or twice daily subcutaneous injection, or orally in the drinking water, was found not to routinely prevent parturition in either the rat or the hamster. However, the duration of labor was prolonged and associated with poor pup viability. The prolonged labor and fetal mortality were thought to be due to suppression of myometrial activity after onset of labor and caused by the episodic administration regimens. Thus fetal deaths could result from asphysia due to suppression of uterine contractions, after partial or total placental separation had occurred. Naproxen was, therefore, administered on a more continuous basis by subcutaneous implantation of pellets in rat and hamster, or orally every four hours in the rat. Either of these regimens was then able to postpone parturition beyond the range of deliveries in control animals. In such naproxen treated rats there was no sign of placetal detachment, even out to day 25 of pregnancy. Fetal viability was preserved and fetuses continued to gain weight. These observations are consistent with a true prolongation of gestation by naproxen rather than merely an interference with the process of labor.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=550150&dopt=Abstract Naproxen Naprosyn





Int J Gynaecol Obstet. 1980 Jan-Feb;17(4):353-4.
Reduction of menstrual blood loss by naproxen in intrauterine contraceptive device users.

Davies AJ.

Eleven patients with objective evidence of menorrhagia (greater than 80 ml menstrual blood loss for two cycles) while fitted with an IUD were treated during three consecutive menstruations with the prostaglandin synthetase inhibitor naproxen. Menstrual blood loss was significantly reduced (p less than 0.001) from a pretreatment value of 131 +/- 12 ml to 88 +/- 9 ml on naproxen therapy. In the cycle following naproxen therapy, menstrual blood loss returned to the pretreatment level of 129 +/- 10 ml. Continued IUD usage was made more acceptable by naproxen therapy.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6102055&dopt=Abstract Naproxen Naprosyn





Br J Clin Pharmacol. 1984 Aug;18(2):207-14.
Naproxen pharmacokinetics in the elderly.

Upton RA, Williams RL, Kelly J, Jones RM.

While naproxen pharmacokinetics appear to be altered in the presence of both diminished renal and hepatic function, the degree to which naproxen disposition might be influenced in the elderly by concurrent alteration in these functions is not obvious. Total plasma clearance/bioavailability (CL/F) of naproxen after a single 375 mg oral dose was found to be less in a group of 10 healthy men between 66 and 81 years of age than in 10 healthy men between 22 and 39 years (0.318 +/- 0.078, 0.416 +/- 0.061 l/h). At steady state (375 mg, 12 hourly), however, CL/F was statistically indistinguishable between the two groups. The fraction of naproxen unbound to plasma protein was doubled in elderly subjects, both at peak and trough drug concentrations. The lowered protein binding tended to obscure a 50% decrement in the intrinsic clearance of naproxen in the elderly as estimated by unbound clearance/bioavailability (213 +/- 64, 396 +/- 155 l/h). As a result, mean steady-state plasma concentrations of naproxen were indistinguishable between the elderly and young (64.2 +/- 8.5, 58.2 +/- 8.1 mg/l) but the elderly generated twice the mean steady-state unbound plasma drug concentration (0.157 +/- 0.039, 0.0859 +/- 0.0212 mg/l). Since it is the unbound drug concentration which appears in general to relate more closely to pharmacological and toxic effect, it may be advisable to reduce naproxen doses by half in the elderly, pending plasma drug concentration-response studies in this age group. If a similar perturbation with age occurs in benoxaprofen protein binding as was observed with naproxen, benoxaprofen intrinsic clearance in the elderly might be only one quarter of that in younger individuals; a factor which may contribute to the toxicity of this drug in the elderly.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6487459&dopt=Abstract Naproxen Naprosyn





Biopharm Drug Dispos. 1984 Jan-Mar;5(1):33-42.
Interaction of naproxen with cholestyramine.

Calvo MV, Dominguez-Gil A.

'In vitro' and 'in vivo' studies were used to determine the interaction of naproxen, an anti-inflammatory agent, and cholestyramine, a hypocholesterolemic substance. Cholestyramine shows a marked affinity for naproxen and the intensity of this is governed by the pH values. The maximum amount of naproxen adsorbed by the resin is close to 2.2 mM g-1. The pharmacokinetics of naproxen was studied in eight healthy volunteers after concurrent oral administration in a single dose of 250 mg of naproxen and 4 g of cholestyramine. The resin causes an important delay in the incorporation of naproxen into the systemic circulation, though no significant modifications are seen to take place in any other pharmacokinetic parameters of the drug.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6704505&dopt=Abstract Naproxen Naprosyn





J Clin Chem Clin Biochem. 1978 Oct;16(10):579-83.
[Fluorometric method for the determination of naproxen and demethylnaproxen in serum and urine (author's transl)]

[Article in German]

Held H.

Naproxen and demethylnaproxen can be determined fluorometrically in serum and urine after extraction with dichlorethane, and without prior separation. The detection limit of naproxen and demethylnaproxen is below 0,2 mg/l in serum and below 0,5 mg/l in urine. After incubation of urine with beta-glucuronidase/arylsulfatase, most of the conjugated naproxen and demethylnaproxen can be determined.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=712339&dopt=Abstract Naproxen Naprosyn





Eur J Clin Pharmacol. 1980 Oct;18(3):263-8.
Pharmacokinetics of naproxen in subjects with normal and impaired renal function.

Anttila M, Haataja M, Kasanen A.

The pharmacokinetics of naproxen after a single oral dose of 250 mg has been studied in 8 subjects with normal renal function and 16 patients with varying degrees of chronic renal insufficiency. Unchanged naproxen and its main unconjugated metabolite, 6-0-desmethylnaproxen, were determined fluorometrically in serum. In healthy subjects the elimination half-life of naproxen was 17.7 +/- 3.0 h (mean +/- SD) and it was not significantly prolonged in patients with renal failure (18.1 +/- 5.3) h. No accumulation of naproxen in serum occurred in uraemic patients. On the contrary, serum drug levels were slightly but significantly lower in patients with severe renal failure. The total body clearance and apparent volume of distribution of naproxen were significantly increased in this group of patients. Decreased binding of naproxen to serum proteins was observed in patients with renal failure. The apparent half-life of desmethylnaproxen was of the same order of magnitude as that of naproxen (18.6 +/- 4.4 h), and was also independent of renal function. A good correlation was found between the area under the curve (AUC), the peak concentration of the metabolite and the serum creatinine concentration. These observations suggest increased metabolism and an increased apparent volume of distribution of naproxen in severe renal failure, probably caused by decreased serum protein binding of the drug. However, it is proposed that in naproxen therapy no adjustment of the dosage regimen is necessary in patients with impaired renal function.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7439246&dopt=Abstract Naproxen Naprosyn





Biochem Pharmacol. 1995 Mar 30;49(7):991-6.
Oxidative stress in isolated rat hepatocytes during naproxen metabolism.

Yokoyama H, Horie T, Awazu S.

Department of Biopharmaceutics, Tokyo College of Pharmacy, Japan.

Naproxen, a non-steroidal anti-inflammatory drug, induced lipid peroxidation in isolated hepatocytes of rats. The viability of the hepatocytes decreased upon lipid peroxidation, and this effect was accompanied by the formation of high molecular weight protein aggregates in the hepatocytes. Protein aggregation occurred slowly compared with the formation of thiobarbituric acid reactive substances (TBARS). The increase of TBARS was strongly correlated with the decrease of intracellular glutathione. Chemiluminescence was produced from the hepatocyte suspension during naproxen metabolism, and was correlated with the formation of TBARS. These results indicate that lipid peroxidation in the hepatocytes was provoked by reactive oxygens produced in the process of naproxen metabolism.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7741771&dopt=Abstract Naproxen Naprosyn