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PubMed2001

LC-1H NMR used for determination of the elution order of S-naproxen glucuronide isomers in two isocratic reversed-phase LC-systems.

The reactive metabolite S-naproxen-beta-1-O-acyl glucuronide was purified from human urine using solid phase extraction (SPE) and preparative HPLC. The structure was confirmed by 600 MHz 1H NMR. Directly coupled 600 MHz HPLC-1H NMR was used to assign the peaks in chromatograms obtained when analysing a sample containing S-naproxen aglycone and the 1-, 2-, 3-, and 4-isomers of S-naproxen-beta-1-O-acyl glucuronide in two simple isocratic reversed phase HPLC-systems. Using mobile phase 1 (50 mM formate buffer pH 5.75/acetonitrile 75:25 v/v) the elution order was: 4-O-acyl isomers, beta-1-O-acyl glucuronide, 3-O-acyl isomers, 2-O-acyl isomers, and S-naproxen aglycone. Using mobile phase II (25 mM potassium phosphate pH 7.40/acetonitrile 80:20 v/v) the elution order was: alpha/beta-4-O-acyl isomers, S-naproxen aglycone, beta-1-O-acyl glucuronide, 3-O-acyl isomers, and alpha/beta-2-O-acyl isomers. In both systems the elution order for the 2-, 3- and 4-O-acyl isomers corresponded with previously published results for 2-, 3-, and 4-fluorobenzoic acid glucuronide isomers determined by reversed phase HPLC-1H NMR (U.G. Sidelmann, S.H. Hansen, C. Gavaghan, A.W. Nicholls, H.A.J. Carless, J.C. Lindon, I.D. Wilson, J.K. Nicholson, J. Chromatogr. B Biomed. Appl. 685 (1996) 113-122]. The alpha-1-O-acyl isomer was found to be present at approximately 3% of the initial S-naproxen-beta-1-O-acyl glucuronide concentration in the glucuronide isomer mixture after 6 h of incubation at pH 7.40 and 37 degrees C. In both HPLC systems it eluted just before the beta-1-O-acyl glucuronide well separated from other isomers. Investigators should consider the possible formation of a alpha-1-O-acyl isomer when studying glucuronide reactivity and degradation.

Chromatography, High Pressure Liquid↗

PubMed2002

Naproxen ophthalmic solution to manage inflammation after phacoemulsification.

PURPOSE: To explore the efficacy and safety of 2 concentrations (0.1% and 0.2%) of sodium naproxen ophthalmic solution in controlling ocular inflammation in patients having phacoemulsification and intraocular lens implantation. SETTING: Service d'Ophtalmologie La Pitie' and Centre Ophtalmologique, Paris, and Clinique Sourdille, Nantes, France; Department of Ophthalmology, University of Lausanne, Switzerland. METHODS: One hundred one patients were randomly treated with naproxen 0.1%, naproxen 0.2%, or diclofenac 0.1% 3 times a day for 30 days starting the day before surgery. Postsurgical ocular inflammation was measured after 1, 10, and 30 days using the Kowa FC-1000 laser flare-cell meter and a conventional slitlamp biomicroscope. Safety parameters were evaluated at the same visits. RESULTS: Naproxen 0.2% ophthalmic solution and diclofenac 0.01% were comparable in controlling postsurgical inflammation. The naproxen was well tolerated. No serious adverse events occurred during the study. CONCLUSIONS: These preliminary results suggest that naproxen ophthalmic solution may be effectively and safely used to control inflammation after uneventful phacoemulsification. Because of the limited number of patients, larger studies are needed to confirm these results.

Anterior Chamber↗

PubMed2001

Hypersensitivity reactions associated with exposure to naproxen and ibuprofen: a cohort study.

The aim of the study was to evaluate the risks of hospitalisation and death due to hypersensitivity reactions associated with the NSAIDs naproxen and ibuprofen, using a record-linkage database for Tayside, Scotland (population 400,000). Cohorts of patients exposed to naproxen (n=54,038) and ibuprofen (n=79,513) were assembled. There were no deaths due to hypersensitivity. There was an increased risk of unvalidated hypersensitivity reactions during periods on-drug versus off-drug in patients exposed to naproxen and ibuprofen. However, after checking medical records, none of the three valid cases of hypersensitivity in the naproxen cohort and neither of the two in the ibuprofen cohort were judged to be due to NSAID exposure. A "worst-case" scenario gave an adjusted rate-ratio of on-drug with naproxen versus on-drug with ibuprofen of 1.63 (0.50, 5.29). The study shows that hypersensitivity reactions associated with NSAID use are rare, and provides no evidence that the risks of hypersensitivity reactions differ between naproxen and ibuprofen.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

In vitro evaluation of acyloxyalkyl esters as dermal prodrugs of ketoprofen and naproxen.

A series of acyloxyalkyl esters of ketoprofen and naproxen were synthesized and investigated as topical prodrugs with the aim of improving the dermal delivery of the drugs. In addition, some hydroxyalkyl esters of ketoprofen and naproxen were synthesized as possible intermediates of acyloxyalkyl prodrugs. All of the prodrugs were more lipophilic than their parent molecules, as evaluated by drug partitioning between 1-octanol and phosphate buffer at pH 7.4 (log Papp). However, their solubilities in aqueous solutions decreased markedly compared with the parent molecules. The prodrugs were stable toward chemical hydrolysis in aqueous solutions (pH 7.4), but were hydrolyzed to the parent drug both in 80% human serum and in human skin homogenate, with half-lives ranging from 4 to 137 min and from 13 to 403 min, respectively. The abilities of the selected naproxen acyloxyalkyl prodrugs to deliver naproxen through excised human skin were evaluated. Generally, the prodrugs showed similar dermal delivery as the parent drug through cadaver skin. In the present series of lipophilic prodrugs of naproxen, the prodrug with the highest aqueous solubility was the most effective prodrug to deliver naproxen through the skin.

Acylation↗

PubMed1993

Low molecular weight proteins as carriers for renal drug targeting: naproxen coupled to lysozyme via the spacer L-lactic acid.

Low molecular weight proteins (LMWPs) are potential carriers for targeting drugs to the kidney. To test whether ester bonds are suitable for the reversible drug conjugation, the antiinflammatory drug naproxen (Nap) was conjugated to the LMWP lysozyme (LYSO) via an ester bond using an L-lactic acid spacer (Nap-lact-LYSO, 1:1:1). The distribution and degradation of the conjugate in rats were compared to those of an equimolar mixture of free drug and LMWP and of a directly coupled conjugate without spacer (Nap-LYSO). The plasma clearance of Nap-lact-LYSO closely resembled that of Nap-LYSO and LYSO itself. Its major accumulation site appeared to be the kidney as demonstrated by extracorporal gamma-camera counting of the LMWP. Renally released naproxen was excreted in the urine as 6-desmethyl-naproxen-sulfate (6-DMN-S). Apparently the kidneys represent the main sites of demethylation and sulfation after administration of the LMWP-coupled drug. In addition, the renal excretion of naproxen (including its metabolites) was significantly delayed and sustained as compared to that after injection of uncoupled naproxen. Using the L-lactic acid spacer LMWP conjugation, the renal selectivity of Nap was increased 5.6 +/- 0.41-fold. Additional in vitro studies with Nap-lact-LYSO revealed that renal generation of the parent drug coincided with formation of low molecular weight catabolites, mainly as naproxen-L-lactic acid-lysine (Nap-lact-Lys). This indicated that in vitro the rate of cleavage of the ester bond is significantly slower than digestion of the carrier backbone itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed2001

A possible mechanism of naproxen-induced lipid peroxidation in rat liver microsomes.

Previous papers from our laboratory report that naproxen and salicylic acid induced lipid peroxidation in rat liver microsomes, however, the mechanism is still unclear. In the present paper, ferrous iron release, nicotinamide-adenine dinucleotide phosphate reduced form (NADPH) oxidation and hydrogen peroxide (H2O2) formation have been measured to find out which mechanisms are involved in naproxen- and salicylic acid-induced lipid peroxidation. While the increase of ferrous iron release was observed with high concentrations of naproxen, salicylic acid did not stimulate ferrous iron release. Neither of these drugs stimulated NADPH oxidation and H2O2 formation. However hexobarbital and perfluorohexane, known as uncouplers of cytochrome P450, stimulated microsomal NADPH oxidation, O2 consumption, H2O2 formation and water (H2O) formation involving four-electron oxidase reaction. These results suggest that ferrous iron release contributes to naproxen-induced microsomal lipid peroxidation and that naproxen and salicylic acid are not uncouplers of cytochrome P450. Apparently H2O2 does not play an important role in naproxen- and salicylic acid-induced microsomal lipid peroxidation.

Animals↗

PubMed1981

Relation of naproxen kinetics to effect on platelet prostaglandin release in men and dysmenorrheic women.

The purpose of our investigation was to determine kinetics of naproxen [(+)-6-methoxy-alpha-methyl-2-naphthaleneacetic acid] relative to its inhibition of PGF 2 alpha release during thrombin-induced platelet aggregation in man after a single oral dose of 250 or 500 mg. Naproxen and its metabolite 6-hydroxy-alpha-methyl-2-naphthaleneacetic acid were measured by high-performance, reversed-phase liquid chromatography with fluorimetric detection. PGF 2 alpha was measured by radioimmunoassay in platelet-rich plasma (PRP). Our subjects were four healthy adult men and five dysmenorrheic women. Peak concentrations of naproxen varied between 26 and 69 microgram/ml and half-lifes varied between 9.5 and 21.9 hr, mean = 16.4 hr +/- 4.4 (SD). Naproxen plasma protein binding exceeded 99.9%. The concentration of the metabolite was less than 1% of naproxen and followed the same plasma concentration profile as the parent compound. The based concentration of PGF 2 alpha varied between 0.13 and 6.3 ng/ml, mean = 1.5 +/- 1.9 ng/ml. With no exception, there was a marked decrease in the PGF 2 alpha concentration in thrombin-stimulated PRP during therapy, and concentration was inversely correlated to the total plasma naproxen concentration.

Adult↗

PubMed2001

Determination of naproxen in pharmaceutical preparations by room-temperature phosphorescence. A comparative study of several organized media.

Different methods for the determination of naproxen by room-temperature phosphorescence (RTP) using organized media such as cyclodextrins (beta-CD and gamma-CD) and micelles (Triton X-100 and sodium dodecyl sulfate) are reported. The inclusion complexes formed between both beta- and gamma-cyclodextrins and naproxen were previously investigated at both acid and basic pH by spectrofluorimetry. In both cases, 1:1 guest-host stoichiometries were established and the corresponding association constants were calculated. Different systems were examined with the purpose of obtaining phosphorescent emission from naproxen solutions, and the best signals were obtained when naproxen was in the presence of beta-CD-cyclohexane-Tl(I), gamma-CD-1,3-dibromopropane, Triton X-100-Tl(I) and SDS-Tl(I), respectively. In all cases, sodium sulfite was used as deoxygenator. The use of an inorganic compound (thallium nitrate) as a heavy-atom source in a cyclodextrin system represents a novel finding. Surface response optimization approaches were carried out to optimize the chemical variables which have an influence on the RTP emission of naproxen. Based on the results obtained, univariate RTP calibration methods for the determination of the analyte in pharmaceutical preparations were satisfactorily developed. In one case, the standard additions method was applied to a mixture of naproxen and the antibiotic tetracycline.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Efficacy and safety of the COX-2 specific inhibitor valdecoxib in the management of osteoarthritis of the hip: a randomized, double-blind, placebo-controlled comparison with naproxen.

OBJECTIVE: Non-steroidal antiinflammatory agents are commonly used to treat pain and inflammation associated with osteoarthritis (OA), but have poor gastrointestinal (GI) tolerability. This study compared the efficacy of the COX-2 specific inhibitor valdecoxib with naproxen and placebo, in treating symptomatic OA of the hip. DESIGN: This multicenter, randomized, double-blind 12-week study compared the efficacy and tolerability of single daily doses of valdecoxib 5 mg and 10 mg with placebo or naproxen 500 mg BID. Efficacy was assessed by Patient's and Physician's Global Assessment of Arthritis, and the WOMAC (Western Ontario and McMasters) OA Individual and Composite Indices. The incidence of adverse events was monitored throughout the study. RESULTS: Valdecoxib was clinically and statistically superior to placebo for Patient's and Physician's Global Assessment of Arthritis and for all WOMAC OA Indices over the 12 week study period (P<or= 0.05). Valdecoxib 10 mg was similar to naproxen in terms of efficacy, and demonstrated greater numerical improvements compared with valdecoxib 5 mg. Valdecoxib 5 mg and 10 mg demonstrated similar tolerability compared to placebo and a lower incidence of GI-related adverse effects compared with naproxen. CONCLUSIONS: Single daily doses of valdecoxib 5 mg and 10 mg were similar to naproxen and superior to placebo, in treating symptomatic OA of the hip. Both doses of valdecoxib were well tolerated and demonstrated improved GI tolerability compared to naproxen.

Aged↗

PubMed2000

Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group.

BACKGROUND: Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis. METHODS: We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers). RESULTS: Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups. CONCLUSIONS: In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.

Adult↗

PubMed2002

Comparison of rofecoxib, celecoxib, and naproxen on renal function in elderly subjects receiving a normal-salt diet.

BACKGROUND: This study compared directly the renal effects of two selective cyclooxygenase (COX)-2 inhibitors (rofecoxib and celecoxib) with naproxen (dual COX-1/COX-2 inhibitor) and placebo in healthy elderly subjects on a sodium-replete diet. METHODS: A total of 67 elderly subjects stabilized in the clinic for weight and urinary sodium on a controlled 200-mEq sodium diet were randomized in a double-blind fashion to receive rofecoxib, 25 mg daily (n = 17); celecoxib, 200 mg twice daily (n = 17); naproxen, 500 mg twice daily (n = 17); or matching placebo (n = 16) for 28 days. Subjects were sequestered in the clinic for the first 14 treatment days on the controlled diet. RESULTS: Daily urinary sodium excretion during the first 72 hours of treatment (primary endpoint) significantly decreased in rofecoxib, celecoxib, and naproxen groups compared with baseline (P < or =.05). Rofecoxib and celecoxib decreases in urinary sodium excretion rates that were comparable with each other, on the basis of predefined boundaries (-39.5 versus -27.1 mEq/d, respectively) and to naproxen (-40.6, mEq/d). Rofecoxib, celecoxib, and naproxen increased mean systolic blood pressure to a similar degree (3.4, 4.3, and 3.1 mm Hg, respectively, versus -1.3 mm Hg for placebo) after 14 days of treatment; small changes also occurred in diastolic blood pressure (0.3, 0.8, and -0.4 mm Hg, respectively, versus -1.4 mm Hg for placebo). Changes from baseline in creatinine clearance, body weight, and urinary potassium excretion among active treatments were similar. After 28 days of treatment, findings were generally consistent with those at 14 days. No subject reported edema or discontinued treatment as the result of an adverse experience. CONCLUSION: In healthy elderly subjects on a sodium-replete diet, the COX-2 inhibitors rofecoxib and celecoxib did not differ from a nonselective nonsteroidal anti-inflammatory drug (naproxen), in influencing renal function as measured by urinary sodium excretion, systolic and diastolic blood pressure, creatinine clearance, or weight change.

Aged↗

PubMed1991

Effects of sodium naproxen eye drops on rabbit ocular inflammation induced by sodium arachidonate.

Sodium naproxen, a reversible competitive inhibitor of cyclooxygenase, is widely used as an anti-inflammatory agent in clinical practice. The purpose of this study was to determine whether eye drops containing 0.5% (w/v) sodium naproxen reduce a number of inflammatory responses produced by sodium arachidonate in the rabbit's eye. Sodium naproxen eye drops successfully reduced the primary signs of ocular inflammation elicited by 0.5% sodium arachidonate on conjunctiva and iris. However, the drug was less effective in reducing conjunctival inflammation induced by 1% sodium arachidonate. Sodium naproxen treatment significantly reduced the levels of prostaglandin E2 (PGE2), polymorphonuclear leukocytes and protein concentration in aqueous humor samples obtained from the eyes of rabbits treated with 0.5% sodium arachidonate whereas aqueous humor levels of leukotriene B4(LTB4) were not found significantly different from control rabbits. Interestingly, PGE2 as well as LTB 4 "de novo" production by corneas and lenses obtained from rabbits sacrificed 2 h after arachidonate and incubation "in vitro" for 20 min were significantly higher in samples taken from controls than in tissues obtained from the eyes treated with sodium naproxen eye drops. Finally, this drug treatment significantly antagonized the rise in intraocular pressure induced by 0.5% sodium arachidonate. Present data suggest that sodium naproxen may be employed topically to prevent ocular inflammatory reactions where the arachidonic acid cascade is activated.

Animals↗

PubMed1996

A six-month double-blind trial to compare the efficacy and safety of meloxicam 7.5 mg daily and naproxen 750 mg daily in patients with rheumatoid arthritis.

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclooxygenase-2 over cyclooxygenase-1. A double-blind parallel-group trial compared meloxicam 7.5 mg once daily (n = 199) with naproxen 750 mg (n = 180) in rheumatoid arthritis. There was no significant difference between the groups regarding the primary efficacy variables (global efficacy assessment by patient and investigator, number of painful/tender and swollen joints) and eight of the ten secondary efficacy endpoints. Only the swollen joint severity index and the number of discontinuations due to lack of efficacy favoured naproxen 750 mg significantly over meloxicam 7.5 mg. Meloxicam was better tolerated in the gastrointestinal (GI) tract, with fewer GI adverse events in the meloxicam-treated group (30.3%) than in the naproxen-treated group (44.7%), where two patients developed ulcers. No ulcers were seen in meloxicam patients. Significantly more patients discontinued due to GI adverse events in the naproxen group. Additionally, there was a significant decrease in haemoglobin and a significant increase in serum creatinine and urea in the naproxen group compared with the meloxicam group. In conclusion, meloxicam 7.5 mg once daily is a promising treatment in rheumatoid arthritis, with efficacy comparable to naproxen 750 mg. Meloxicam has the advantage of a significantly lower incidence of GI and renal side effects.

Adult↗

PubMed1999

Naproxen in the prevention of heterotopic ossification after total hip replacement.

The effectiveness of naproxen, indomethacin, and a placebo were compared for the prevention of heterotopic ossification after total hip arthroplasty. Eighty-four men at high risk of experiencing heterotopic ossification received randomly either naproxen 750 mg per day, indomethacin 75 mg per day, or a placebo for 6 consecutive weeks after surgery. Efficacy analysis showed that in 70% of patients treated with naproxen, in 34.8% of those treated with indomethacin, and in 15% of those treated with a placebo, no heterotopic ossification appeared on radiographs taken at 6 months. Naproxen was significantly more effective than the placebo or indomethacin in preventing the development of heterotopic ossification. Stratification into five categories, according to Brooker's classification at 6 months, showed that both drugs were equally superior to the placebo. Class III heterotopic ossification occurred only in patients who were given the placebo. The improvement in clinical criteria was comparable in the three groups, although at 6 months there was an improvement in abduction in patients treated with indomethacin compared with those treated with naproxen and the placebo. The overall tolerance was rated good by 87% of patients and 86% of physicians, with no difference between the groups. The results show that naproxen, given daily for 6 weeks, is an effective and safe medication for the prevention of heterotopic ossification after total hip replacement.

Aged↗

PubMed1998

Effect of over-the-counter dosages of naproxen sodium and acetaminophen on plasma lithium concentrations in normal volunteers.

Prescription doses of nonsteroidal antiinflammatory agents have been shown to decrease clearance and increase plasma concentrations of lithium. This study was designed to evaluate whether over-the-counter (OTC) doses of naproxen sodium or acetaminophen have the same potential to affect lithium concentration. This was a prospective, crossover, 3-phase study conducted at the Clinical Pharmacology Studies Unit of the Albany Medical Center Hospital during July and August of 1995. The 3-phase study comprised the following: phase 1, lithium carbonate (300 mg every 12 hours) alone for 7 days; phase 2, lithium and either naproxen sodium (220 mg every 8 hours) or acetaminophen (650 mg every 6 hours) for 5 days; and phase 3, a 2-day washout period followed by a crossover to lithium with the alternate drug (acetaminophen or naproxen sodium) for 5 days. Twelve healthy male volunteers were recruited, nine of whom completed the study and were included in the statistical analysis. Mean (+/-SD) plasma lithium concentrations for subjects in treatment group 1 (lithium in phase 1, lithium and naproxen sodium in phase 2, lithium and acetaminophen in phase 3) were 0.38 (+/-0.11), 0.40 (+/-0.07), and 0.36 (+/-0.11) mEq/L, respectively. Mean plasma lithium concentrations for subjects in treatment group 2 (lithium in phase 1, lithium and acetaminophen in phase 2, lithium and naproxen sodium in phase 3) were 0.43 (+/-0.05), 0.48 (+/-0.10), and 0.48 (+/-0.05) mEq/L, respectively. One-way repeated-measures analysis of variance and paired t-test showed no statistically significant differences (p>0.05) in plasma lithium concentrations during any phase of the study. The results of this study demonstrated that OTC doses of naproxen sodium and acetaminophen did not increase plasma lithium concentrations in these volunteers when taken for short periods of time.

Acetaminophen↗

PubMedDate not supplied

Effects of Cetyltrimethylammonium naproxenate on the adherence of Gardnerella vaginalis, Mobiluncus curtisii, and Lactobacillus acidophilus to vaginal epithelial cells.

BACKGROUND AND OBJECTIVES: A decreased concentration or total disappearance of Lactobacillus acidophilus in the vagina constitutes a frequent observation in bacterial vaginosis. GOAL OF THE STUDY: Cetyltrimethylammonium naproxenate has been evaluated in vitro to detect antiadhesive properties at subinhibitory concentrations for Gardnerella vaginalis and Mobiluncus curtisii to vaginal epithelial cells (VEC). STUDY DESIGN: Bacterial strains 14C- and or 3H-labeled were tested for adherence and competition to binding sites in VECs before and after treatment at sub-MIC with cetyltrimethylammonium naproxenate. RESULTS: In control tests of adherence, G. vaginalis and M. curtisii had their maximal adhesion at pH 5.4, L. acidophilus at pH 4.4. Preincubation of G. vaginalis and M. curtisii with cetyltrimethylammonium naproxenate 2.5 mg/mL (subinhibitory concentration) at pH 5.4 reduced adherence to VECs respectively by 48.3% and 34.1%. The same treatment of L. acidophilus showed no statistically significant difference. Treatment of VECs alone did not modify adherence. Competition tests between L. acidophilus and G. vaginalis and between L. acidophilus and M. curtisii showed that, in small quantities, L. acidophilus could compete with G. vaginalis and M. curtisii for binding sites in VECs at pH 4.4, when pretreated with cetyltrimethylammonium naproxenate. At a higher pH (4.8 and 5.4), L. acidophilus in higher quantities did not compete for binding sites occupied by G. vaginalis and M. curtisii. CONCLUSIONS: Cetyltrimethylammonium naproxenate at subinhibitory concentrations modifies the adhesiveness of G. vaginalis and M. curtisii to VECs, reducing it by 48.3% and 34.1%, respectively. Adhesion of L. acidophilus to VECs is not impaired by pretreatment with cetyltrimethylammonium naproxenate at pH 4.4, even if they are in low number and compete for binding sites against pathogens. At higher pH levels, L. acidophilus did not compete for binding sites occupied by G. vaginalis and M. curtisii.

Adult↗

PubMed1981

Effect of naproxen on glucose metabolism and tolbutamide kinetics and dynamics in maturity onset diabetics.

1 The influence of the nonsteroidal anti-inflammatory drug naproxen on glucose metabolism and on tolbutamide pharmacokinetics and pharmacodynamics has been studied in ten maturity-onset diabetics. 2 Comparison of both plasma glucose decay curves and insulin responses during an intravenous glucose tolerance test before and after eight 12 hourly doses of naproxen revealed that naproxen had no significant influence on fasting glucose levels or on rates of glucose elimination. 3 When the subjects were given a combination of naproxen and tolbutamide for 3 days naproxen had no influence on tolbutamide absorption, protein binding, disposition or pharmacological effect. 4 Treatment with tolbutamide in maturity-onset diabetics need not be modified if concurrent administration of naproxen is contemplated.

Adult↗

PubMed1986

Double-blind multicentre UK hospital studies of isoxicam vs naproxen.

1 Two multicentre, parallel group, randomised, double-blind, double-dummy comparison studies were conducted between isoxicam in the usual dose of 200 mg once daily and naproxen 500 mg twice daily. 2 The drugs were administered for 4 weeks to 230 patients suffering from osteoarthritis of the hip and/or knee in the first trial and to 249 patients suffering from rheumatoid arthritis in the second. 3 The studies compared treatments for both safety and overall effectiveness in the relief of pain. 4 In the osteoarthritis trial, overall pain was reduced by both drugs after 2 weeks of therapy but only isoxicam produced further improvement after 4 weeks. 5 Isoxicam produced reductions comparable to those produced by naproxen in pain on standing from the sitting position, pain on walking, and pain on movement of the affected joint, after 2 and 4 weeks. 6 After 4 weeks, isoxicam given once daily in the morning was significantly more effective than naproxen given in the morning and the evening in relieving not only total pain as assessed by a visual analogue scale but, as importantly, night pain. 7 Compared to naproxen therapy, isoxicam therapy was associated with significantly more patients whose disease state was improved at 2 weeks, as assessed by physicians. 8 In the rheumatoid arthritis trial, isoxicam was equally as effective as naproxen in reducing joint tenderness, joint swelling, and pain; at 4 weeks there was a trend in favour of isoxicam in reduction of joint swelling and pain. 9 Isoxicam reduced morning stiffness significantly more than naproxen after 4 weeks; this trend was apparent at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗