J Pediatr. 1994 Apr;124(4):639-42.
Naproxen-induced pseudoporphyria in patients with juvenile rheumatoid arthritis.

Lang BA, Finlayson LA.

Izaak Walton Killam Children's Hospital, Department of Pediatrics, Halifax, Nova Scotia, Canada.

Pseudoporphyria, a cutaneous disorder characterized by skin fragility, vesiculation, and scarring, has been reported as a side effect of naproxen therapy in children with juvenile rheumatoid arthritis (JRA). We report the results of a 6-month prospective study to determine the prevalence of pseudoporphyria in our JRA population. All the patients with pseudoporphyria had received naproxen for > or = 4 weeks at the time of the study. Of the patients treated with naproxen, 12% (9/74) developed this complication. No patient had significant elevation of free erythrocyte protoporphyrin, excluding the diagnosis of true erythropoietic protoporphyria. We conclude that pseudoporphyria is a common side effect of naproxen therapy in children with JRA, even in geographic areas without high sun exposure. Because of the risk of facial scarring with pseudoporphyria, physicians and parents of children with JRA should be aware of this complication.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8151484&dopt=Abstract Naproxen Naprosyn





Am J Gastroenterol. 1991 Jun;86(6):735-7.
Effect of Helicobacter pylori infection on the severity of gastroduodenal mucosal injury after the acute administration of naproxen or aspirin to normal volunteers.

Lanza FL, Evans DG, Graham DY.

Baylor College of Medicine, Division of Gastroenterology Houston, Texas.

This study asked whether Helicobactor pylori infection accentuated the severity of NSAID-induced mucosal injury of the stomach or duodenum. We evaluated the severity of acute mucosal injury and H. pylori status in 61 normal volunteers (ages 22-43 yr) receiving naproxen (1000 mg, n = 30) or aspirin (3900 mg, n = 31) daily for 7 days. NSAID-induced gastric and duodenal mucosa each were endoscopically graded separately for hemorrhages and erosions-ulcers on a scale of 0 to 4. H. pylori infection was identified by a sensitive and specific ELISA. Nine of the 30 subjects in the naproxen group and 12 of the 31 subjects in the aspirin group were H. pylori positive (p = NS). There was no statistically significant difference between the frequency of mucosal hemorrhage in those with and those without H. pylori infection (44% compared with 33% for those receiving naproxen and 90% of those receiving ASA, p = NS for each). There were also no differences in the frequency or severity of erosive mucosal injury seen, e.g., acute ulcers were found in 16.5% and 17.5% of infected and uninfected subjects, respectively. We conclude that the presence of H. pylori infection does not influence the degree or type of mucosal damage associated with the acute administration of naproxen or aspirin.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2038996&dopt=Abstract Naproxen Naprosyn





Biol Reprod. 1992 Jan;46(1):58-64.
Myometrial oxytocin receptors and prostaglandin in the parturition process in the rat.

Chan WY, Chen DL.

Department of Pharmacology, Cornell University Medical College, New York, New York 10021.

Parturition in rats is associated with an abrupt and marked increase in myometrial oxytocin (OT) receptor concentrations. In this study, we investigated the role of myometrial OT receptors in the initiation and the process of parturition. We produced chronic OT receptor blockade during the last 3 days of gestation by administration of a specific OT antagonist at 100 micrograms/day and 300 micrograms/day. We also suppressed OT receptor formation by inhibiting prostaglandin synthesis with naproxen sodium at 2 mg/day and 5 mg/day. We found that chronic blockade of OT receptors inhibited the uterotonic response to OT in Day 22 and Day 23 pregnant rats in a dose-dependent manner. OT antagonist treatment did not prolong the gestation period. However, the duration of parturition, fetal mortality, and the mortality incidence were increased in rats treated with the high dose of the OT antagonist compared to controls. Naproxen sodium at both dosage levels prolonged gestation by 24 h or longer, doubled the duration of parturition, and markedly increased fetal mortality and mortality incidence. Combined OT antagonist and naproxen treatment produced adverse outcomes similar to that produced by naproxen treatment alone. Myometrial OT receptor concentrations were markedly increased in all rats immediately postpartum, ranging from 210 to 425 fmol/mg protein compared to the 50 to 100 fmol/mg found in Day 21 and Day 22 pregnant rats. Correlation analyses between OT receptor concentrations and various parameters associated with gestation and parturition showed that there was a correlation between low OT receptor concentrations and long gestation period, prolonged parturition, and high fetal mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS)

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Am J Obstet Gynecol. 1984 Dec 15;150(8):1000-1.
Naproxen sodium for pain relief in first-trimester abortion.

Suprapto K, Reed S.

PIP: The analgesic efficacy of naproxen sodium was compared with that of a placebo or of no drug in 137 women undergoing 1st-trimester elective abortion. 46 women received a single 550 mg dose of naproxen sodium 1-2 hours prior to abortion, 46 women received a placebo, and 45 women received no drug. Abortions were performed by means of suction curettage after anesthesia was produced by paracervical block with 1% lidocaine solution, and study subjects were asked to assess their pain on a scale from 0-99 at the most painful moment during abortion and at 15 and 30 minutes after abortion. Pain scores reported by naproxen sodium patients were consistently lower than those reported by placebo and no drug patients, and the difference between average pain scores of naproxen sodium patients and placebo patients was statistically significant at each evalution. Pain scores of untreated patients were comparable to those of placebo patients. Multiparous and multigravid women reported lower pain scores than women who had never been pregnant before. There were no apparent side effects of naproxen sodium treatment. These findings indicate that naproxen sodim can provide effective analgesia for pain caused by uterine contractions during and after suction abortion. Its terapeutic effectiveness may be enhanced by administration 1-2 hours prior to he abortion procedure so that peak plasma concentrations are attained.

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J Rheumatol. 1993 Sep;20(9):1472-7.
Histologic changes in rheumatoid synovitis induced by naproxen and methotrexate.

Balsa A, Gamallo C, Martin-Mola E, Gijon-Banos J.

Rheumatology Unit, Hospital La Paz, Madrid, Spain.

OBJECTIVE. To study the changes in rheumatoid synovitis induced by the nonsteroidal antiinflammatory drug (NSAID), naproxen, and methotrexate (MTX). METHODS. Twelve patients were treated with naproxen, and 11 with MTX and a clinical activity index was measured before and after treatment. A synovial biopsy was taken, on entry into the study and after 73 +/- 43 days in the NSAID group and 145 +/- 35 in the MTX group. Synovial cells bearing CD3, CD4, CD8, CD19, LeuM5 (CD11c), HLA-DR, HLA-DP and CD25 antigens were measured by stereology. RESULTS. Patients treated with MTX showed a reduction in the number of CD3+ (p = 0.01), CD4+ (p = 0.007) and HLA-DR+ (p = 0.01) cells with an improvement in the activity index (p = 0.001). The patients treated with naproxen did not show changes in the activity index or in the synovial infiltrate. CONCLUSION. Our findings support the theory that clinical improvement in rheumatoid synovitis is associated with a significant decrease in the number of T cells infiltrating the synovial membrane.

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Drug Metab Dispos. 1991 Mar-Apr;19(2):304-8.
Stereoselective (S)- and (R)-naproxen glucuronosyl transferases of rat liver.

el Mouelhi M, Bock KW.

Institute of Toxicology, University of Tubingen, FRG.

Stereoselective glucuronidation of naproxen, one of the 2-arylpropionic acids that are widely used as anti-inflammatory drugs, was investigated in chromatofocusing fractions of solubilized liver microsomes from 3-methylcholanthrene- (MC) and phenobarbital- (PB) treated rats. On chromatofocusing of solubilized microsomes of PB-treated rats, two naproxen glucuronosyltransferase (GT) fractions were separated. The fraction eluting at pH 8.7 preferentially conjugated (S)-naproxen (S/R ratio = 1.6) and the fraction eluting at pH 7.8 mostly conjugated (R)-naproxen (S/R ratio = 0.7). Chromatofocusing of solubilized microsomes from MC-treated rats also resulted in the separation of two naproxen GT fractions, eluting at pH 9.4 (S/R ratio 0.2) and at pH 8.7 (S/R ratio 0.8). These two fractions coincided with the elution of known MC-inducible GT activities assigned to a GT isozyme variously termed 4-nitrophenol GT or GT-I. Interestingly, kidney microsomes, known to contain a high constitutive expression of GT-I, preferentially glucuronidated (R)-naproxen (S/R ratio 0.2). The S/R ratio of 0.8, observed with the pI 8.7 fraction of MC-treated rat liver, may be explained by the presence of a mixture of naproxen GTs, consisting of (R)-naproxen GT (S/R ratio 0.2) and of (S)-naproxen GT (S/R ratio 1.6). The results suggest that naproxen is conjugated by at least 3 GT isozymes in rat liver; these have been operationally designated (S)-naproxen GTPB (S/R ratio 1.6), (R)-naproxen GTPB (S/R ratio 0.7), and (R)-naproxen GTMC (S/R ratio 0.2). The latter isozyme is probably identical to the previously characterized MC-inducible GT-I. Thus, (S)- and (R)-naproxen represent useful substrates to distinguish different GT isozymes.

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Arthritis Rheum. 1987 Oct;30(10):1157-61.
Serum concentrations of salicylate and naproxen during concurrent therapy in patients with rheumatoid arthritis.

Furst DE, Sarkissian E, Blocka K, Cassell S, Dromgoole S, Harris ER, Hirschberg JM, Josephson N, Paulus HE.

Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City.

The kinetic interaction between salicylate and naproxen was investigated in 25 rheumatoid arthritis patients. Kinetic interactions were tested in serum after patients had been on each drug regimen for 1 month. Salicylate decreased serum naproxen concentration from 89.5 mg/liter to 65.9 mg/liter (P less than 0.001) and increased serum naproxen clearance by 56%. Naproxen had minimal effect on serum salicylate concentrations.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3675660&dopt=Abstract Naproxen Naprosyn