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PubMed1995

Relationship between naproxen plasma concentration and its anti-inflammatory effect in experimental hepatitis.

The relationship between the plasma concentration and the anti-inflammatory effect of naproxen (CAS 22204-53-1) after oral administration of a 6 mg.kg-1 dose was studied in rats with galactosamine-induced acute hepatitis and under control conditions. In control animals naproxen peak plasma levels of 35 +/- 0.4 micrograms.ml-1 were reached in 0.5 +/- 0 h. Concentration then decayed, half-life being 5.2 +/- 0.4 h. AUC was 131 +/- 5 micrograms.h.ml-1. In intoxicated rats peak plasma levels of 29 +/- 0.3 micrograms.ml-1 were reached in 0.7 +/- 0.1 h, half-life was increased to 11.1 +/- 1.3 h, and the AUC reached 259 +/- 21 micrograms.h.ml-1. In control rats the protective effect of naproxen against carrageenan-induced inflammation increased slowly, reaching a maximum of 38% in 4 h. The protective effect against plasma concentration curve exhibited a clear counterclockwise hysteresis, probably due to a slow naproxen transport from the circulation to its site of action. In animals with hepatitis, the protective effect remained quite constant at about 40% despite variations in plasma levels, probably because the maximal effect was reached. No clear hysteresis was observed in the effect-plasma concentration curve, suggesting that naproxen arrival to its site of action was faster. Results show that the relationship between naproxen plasma concentration and its anti-inflammatory effect is complex and therefore predictions on the pharmacological response in liver damage cannot be readily made by solely considering pharmacokinetic data.

Animals↗
PubMed1995

Naproxen for 8 days can prevent heterotopic ossification after hip arthroplasty.

The effect of 1 week of treatment with naproxen on the formation of heterotopic ossification after cemented total hip arthroplasty was studied in a prospective trial. Twenty-seven patients received 500 mg naproxen twice daily for 7 days postoperatively. The medication was started on the morning of the operation. The results were compared with a control group of 23 patients from a previous study who had not received any type of non-steroidal antiinflammatory drug. All radiographs were mixed randomly, and patient identification was blinded. Three months after the operation, heterotopic ossification had developed in 12 (52%) patients in the control group and in 3 (11%) patients in the naproxen-treated group. One year after the operation, 4 (17%) patients in the naproxen-treated group and 12 (52%) in the control group had heterotopic ossification (p < 0.05). Severe ossification developed in 3 patients in the control group and in none in the naproxen-treated group. The authors conclude that naproxen given for 1 week can decrease the incidence of heterotopic ossification after total hip arthroplasty.

Adult↗
PubMed1994

A longterm endoscopic evaluation of patients with arthritis treated with nabumetone vs naproxen.

OBJECTIVE: To compare the gastrointestinal safety, ulcerogenic potential, and clinical efficacy over 5 years of nabumetone and naproxen therapy, in patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: Fifty-two patients entered a randomized, double blind study. Patients were randomized to 3 months treatment with either nabumetone, 1000 mg nightly, or naproxen, 250 mg twice daily, followed by an endoscopist-blind 5-year followup study. After the double blind phase, 15 patients in the nabumetone group and 12 in the naproxen group continued in the longterm endoscopist-blind phase. Endoscopic evaluations for gastroduodenal damage and global assessments of arthritis activity and degree of pain for efficacy were measured. RESULTS: Over the 5-year period, endoscopically visible gastroduodenal ulceration was found in 8 of the naproxen treated patients compared with one of the nabumetone treated patients (p = 0.02). There was a significant difference in the time to develop an ulcer, with a greater risk of developing an ulcer sooner while taking naproxen (p < 0.01). Patients in both groups reported significant improvements in arthritis symptoms (p < 0.01). CONCLUSION: Nabumetone appears to have a significantly lower ulcerogenic potential than naproxen over a 5-year period, and there is a trend toward better tolerability as measured by withdrawals for adverse experiences.

Aged↗
PubMed1975

Long-term clinical assessment of naproxen on rheumatoid arthritis patients and 51-Cr gastrointestinal bleeding on volunteers.

64 patients with rheumatoid arthritis (R.A.) entered the trial: 40 of them still remain on medication; 28 have so far completed 2 years; 23, 3 years; 12, 4 years using D-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) as the principal anti-inflammatory agent. Tolerance has been good: side effects or complaints, when reported, were mild and transient in nature. Close monitoring of a range of biochemical values by sequential laboratory studies has not revealed naproxen to have many adverse effects. After two years of daily continuous naproxen administration, 19 volunteer patients were subjected to a short-term double-blind cross-over placebo experiment. The results were in favor of a continued therapeutic efficacy of naproxen. The possible gastrointestinal bleeding found in the majority of anti-inflammatory drugs has been studied on 12 volunteers using 51-Cr. Naproxen exhibited a mean G.I. blood loss comparable to placebo or to physiological blood loss in normal volunteers. The conclusion drawn is that naproxen shows a good therapeutic index.

Adult↗
PubMed1975

Clinical and objective assessments of naproxen through 5 years of clinical experience.

D-2-(6'-Methoxy-2'-naphthyl)-propionic acid (naproxen) is a relatively well-known non-hormonal anti-inflammatory agent useful for long-term usage. The efficacy of naproxen in controlling the signs and symptoms of rheumatoid arthritis had been uniformly demonstrated in an extensive series of international double-blind trials lasting from a few weeks to four months. This paper deals with our experience with naproxen after 5 1/2 years of continuous usage. During this period of time ten different studies were conducted at the Rheumatology Departments of the General Hospital, Mexico City. The efficacy and tolerance of naproxen have been studied in the following indications: rheumatoid arthritis, osteoarthritis, acute and chronic gout and non-articular rheumatism. In these studies the usual clinical methods were used and some special objective methods were utilized in some others, for example, enzymology, scintigraphy, histopathology and arthroscopy. Some of these studies were comparative ones vs. some other well-known non-steroidal anti-inflammatory compounds such as aspirin, indometacin and ibuprofen. During the last 5 1/2 years 877 patients with different theumatic conditions were treated and observed in our Department and in the private practice. In 365 patients with rheumatoid arthritis excellent results were obtained in 34%, good in 36%, fair in 24% and negative in only 6%. In 358 patients with osteoarthritis excellent results were obtained in 28.2%, good in 46.6%, fair in 20% and negative in 5.3%. In 15 patients with acute gout using naproxen as exclusive therapy, excellent results were observed in nine patients very good in four, and unsatisfactory in only two cases. In 35 patients with chronic gout excellent results were observed in 22, good in 11 and negative in two. 93 patients out of the 877 studied since June 1969 used naproxen continuously as anti-rheumatic therapy for more than one year; 33 for more than two years; four patients for more than three years and five of the patients in a few days will complete 5 1/2 years. The side effects of the compound observed during this long period of time in these 877 patients on the g.i. tract, CNS, etc., although present in a limited number of cases (in less than 10% of total number of patients) were definitely less than those observed usually during anti-inflammatory therapy.

Adolescent↗
PubMed1994

[Fast-dissolving sublingual tablets of piroxicam versus naproxen in the treatment of recurrent acute osteoarthrosis. Multicenter clinical trial].

An open comparative study was carried out to evaluate the efficacy and safety of piroxicam FDDF, for sublingual administration, versus naproxen in the treatment of osteoarthritis. Sixty-one patients with acute-phase osteoarthritis involving various joints are reported. They were treated with 20 mg/day piroxicam FDDF or with 1000 mg/day naproxen for a total of 4 weeks. Drug efficacy was evaluated on the base of the variation of spontaneous pain, pain on motion, functional limitation and capacity to perform a specific activity. The intensity of spontaneous pain on the first day showed a statistically significant improvement with both drugs, but the onset of analgesia was only after 15 minutes with piroxicam and after 1 hour with naproxen. The improvement in pain intensity increased on the first day and until the 7th day with both drugs, but the comparative analysis between the analgesic efficacy of the two treatments proved to be favourable to piroxicam. On the 7th day, pain on motion and the capacity to perform a specific activity showed a statistically significant improvement with both drugs, but the comparative analysis between the two treatments proved to be favourable to piroxicam. The two drugs showed the same efficacy in functional restriction. The local and systemic tolerability of piroxicam was good. Only 5 patients experienced 6 systemic side-effects, and 1 patients showed local side-effects, but 11 patients of the naproxen group showed 12 systemic side-effects. Thus piroxicam showed a better analgesic and anti-inflammatory efficacy than naproxen. Piroxicam proved to have a better systemic tolerability than naproxen. The local tolerability of piroxicam FDDF was good.

Acute Disease↗
PubMed1993

Pain relief following day-case diagnostic hysteroscopy-laparoscopy for infertility: a double-blind randomized trial with preoperative naproxen versus placebo.

OBJECTIVE: To study the effects of preoperative naproxen on postoperative and post-discharge outcome and consumption of analgesics in patients undergoing diagnostic hysteroscopy and laparoscopy for infertility. METHODS: A double-blind, placebo-controlled study was conducted in 60 healthy women scheduled for day-case hysteroscopy and laparoscopy. Subjects were randomized to receive either 500-mg naproxen suppositories (n = 30) or placebo (n = 30) preoperatively. Following discharge, each patient was given two naproxen suppositories for treatment of pain at home. Pain was scored on the Visual Analogue Scale, and the postoperative and post-discharge use of analgesics was determined, recorded, and analyzed. RESULTS: Patients premedicated with naproxen had significantly less postoperative pain, showed more rapid ambulation, could be discharged earlier, and had less post-discharge pain. On the day after surgery, only six of 28 naproxen-treated patients needed analgesics, compared to 18 of 30 placebo patients. CONCLUSION: Day-case diagnostic hysteroscopy and laparoscopy for evaluation of infertility is potentially painful and stressful. Preoperative naproxen contributed to postoperative pain prevention, reduced hospital stay and consumption of analgesics, and shortened the period of post-discharge abdominal discomfort.

Ambulatory Surgical Procedures↗
PubMed1993

[A comparative evaluation of the remission from acute lumbar-sciatic pain following treatment with meclofenamic acid and naproxen].

This study was performed to assess the analgesic effect and the onset of action of meclofenamic acid compared with naproxene in patients affected by acute lumbar-sciatic pain. Thirty patients of both sexes were randomly allocated to 2 groups of 15 patients each; the first group was treated with meclofenamic acid (200 mg b.i.d.) and the second with naproxene (500 mg b.i.d.). Both drugs were administered as suppositories for a week. The intensity of pain, both at rest and after movement, was assessed by means of analogic scales at basal time and 15, 30, 60, 180, 360 minutes, 4 and 8 days after the first administration. Both types of pain were significantly decreased with respect to basal values in meclofenamic acid group (P < 0.01), 60 minutes after onset of treatment, while in the naproxene group the effect was later. Moreover the analgesic effect was significantly greater in the meclofenamic acid group with respect to the naproxene group, after 15 minutes for pain at rest (P < 0.05) and after 30 minutes for pain after movement (P < 0.02). Similarly, after 4 and 8 days, both types of pain improved to a larger extent in the meclofenamic acid group with respect to the naproxene group (P < 0.05 after four days and P < 0.01 after eight days). This study has shown that meclofenamic acid has greater efficacy and faster analgesic effect than naproxene. Meclofenamic acid has proved to be a drug of choice in the treatment of slight to moderate musculo-skeletal pain syndromes.

Acute Disease↗
PubMed1995

Plasma and synovial fluid kinetics, disposition, and urinary excretion of naproxen in horses.

Naproxen (+6-methoxy-[alpha-methyl]-2-naphthalene acetic acid) is a nonsteroidal anti-inflammatory drug that is used for the treatment of inflammatory conditions in horses. We developed a model that describes the drug's disposition and renal excretion, including synovial fluid disposition and elimination after IV administration in horses. The plasma disposition, after IV administration of 5 mg/kg of body weight, was described by a two-compartment model; mean +/- SD distribution and elimination half-lives were 1.42 +/- 0.42 and 8.26 +/- 2.56 hours, respectively. Plasma concentration of naproxen after IV administration of 5 mg/kg was 55.3 +/- 13.5 and 0.61 +/- 0.42 mg/L at 5 minutes and 48 hours after its administration, respectively. Steady-state volume of distribution was 0.163 +/- 0.053 L/kg, and area under the plasma concentration time-curve was 372.1 +/- 128.2 mg/h/L. The peak synovial fluid concentration of 12.68 +/- 12.39 mg/L was measured at 6 hours, and decreased to 0.71 +/- 0.38 mg/L at 36 hours after naproxen administration. The decrease of naproxen concentration in synovial fluid paralleled that in plasma. The appearance half-life of naproxen in synovial fluid was 4.64 hours, and the elimination half-life was 6.73 hours. Total body clearance was 0.015 +/- 0.006 L/h/kg. The percentage of plasma protein binding was 97.0 +/- 2.9% at plasma concentrations between 5 and 100 mg/L. This was significantly (P < 0.05) higher than the percentage of binding at plasma concentrations of 0.5, 1, and 500 mg/L, which was 75.2 +/- 11.8%. Most of the drug was excreted as glucuronidated naproxen and unconjugated desmethylnaproxen.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1996

The relationship between the content of aggressive and protective components in gastric juice and endoscopic findings after naproxen sodium and acetaminophen administration.

OBJECTIVES: To evaluate the diagnostic value of residual gastric juice, we assessed various secretory components before and after placebo, acetaminophen, or naproxen sodium administration. METHODS: In a double-blind, randomized, cross-over study in 30 asymptomatic volunteers, mucin, hydrophobicity, protein, pepsin, and pH were measured in residual gastric juice before and after placebo, naproxen sodium (660 mg/d), or acetaminophen (4000 mg/d) administration. Mucus layer thickness in biopsy specimens was assessed, and mucosal damage was endoscopically evaluated. RESULTS: All parameters were unchanged after 7 days of placebo. Naproxen caused a 46% (p = 0.008) increase in the rate of luminal mucin release, an 18% increase (p = 0.510) in protein release, and a 61% decrease (p = 0.001) in hydrophobicity. Antral and duodenal mucus gel thickness were compromised, and hemorrhagic and erosive endoscopic changes were noted. Acetaminophen resulted only in a significant decline of pepsin. In subjects without endoscopic damage after naproxen, a nonsignificant decrease in hydrophobicity was noted. However, in subjects with endoscopic changes, a 55% decrease (p = 0.002) in hydrophobicity and a 42% increase (p = 0.024) in the rate of luminal mucin release were demonstrated. The initial mucin of subjects who developed endoscopic mucosal changes after naproxen was 53% higher than in subjects without damage. Subjects with endoscopic changes also exhibited a 48% lower initial hydrophobicity and a 43% lower pepsin than subjects without endoscopic changes. CONCLUSIONS: Gastric mucosal damage after naproxen sodium results in profound changes within the gastric mucosal barrier, and analysis of residual gastric juice components adequately reflects these changes. In contrast, acetaminophen results in only minimal gastric juice changes. Analysis of residual gastric juice may be useful in monitoring the extent of mucosal damage and identifying patients likely to develop mucosal damage.

Acetaminophen↗
PubMed1996

Prostaglandin E2 content in residual gastric juice reflects endoscopic damage to the gastric mucosa after naproxen sodium administration.

OBJECTIVES: The diagnostic potential of residual gastric juice for development of naproxen sodium-induced mucosal damage has not been explored. We studied prostaglandin E2 (PGE2) content in residual gastric juice before and after naproxen sodium administration and assessed relationships with endoscopic mucosal damage. METHODS: Thirty volunteers received the recommended over-the-counter dose (660 mg/day) of naproxen sodium or placebo in this 7-day, double-blind, endoscopically controlled, cross-over study. RESULTS: PGE2 concentration in gastric juice did not increase after placebo; naproxen significantly reduced PGE2 concentration (p < 0.001). In three subjects in whom no endoscopic changes occurred after naproxen administration, PGE2 concentration increased by 14%. In seven subjects who developed hemorrhagic changes, PGE2 concentration declined by 50% (p = 0.08). In 20 subjects who developed numerous hemorrhagic and erosive changes within the antral mucosa, PGE2 concentration declined by 70% (p < 0.001). The starting PGE2 value in subjects with severe mucosal hemorrhagic and erosive changes after naproxen was almost eightfold higher than in subjects who did not develop mucosal damage (p = 0.007) and 67% higher than in subjects with hemorrhagic changes only (p = 0.25). CONCLUSION: PGE2 measurement in residual gastric juice, aspirated before and after nonsteroidal antiinflammatory drug treatment, may be useful in monitoring mucosal damage and may identify patients who are likely to develop endoscopic mucosal changes.

Adult↗
PubMed1996

[Eight days of naproxen therapy can prevent heterotopic ossification after total hip alloplasty].

The effect of one week of treatment with naproxen on the formation of heterotopic ossification after cemented total hip arthroplasty was studied in a prospective trial. Twenty-seven patients received 500 mg naproxen twice daily for seven days postoperatively. The medication was started on the morning of the operation. The results were compared to a control group of 23 patients from a previous study who had not received any kind of nonsteroidal anti-inflammatory drug. All radiographs were randomly mixed and patient identification was blinded. Three months after the operation 12/23 patients in the control group and 3/27 in the naproxen-treated group had developed heterotopic ossification. One year after the operation 4/27 in the naproxen-treated group and 12/23 in the control group had heterotopic ossification (p < 0.05). Three patients in the control group and none in the naproxen-treated group developed severe ossification. It is concluded that naproxen given for one week can decrease the incidence of heterotopic ossification after total hip arthroplasty.

Aged↗
PubMed1995

Stereoselective disposition of naproxen glucuronide in the rat.

The disposition of R- and S-naproxen glucuronides were investigated after intravenous administration (approximately 1.5 mg/kg) to normal male Sprague-Dawley rats and to rats pretreated with phenylmethylsulfonylfluoride, an inhibitor of esterases. The relative stability of the two glucuronides also was measured in vitro. Both diastereomers were hydrolyzed rapidly in vivo, liberating naproxen, but R-naproxen glucuronide was hydrolyzed faster than the corresponding S-diastereomer. This difference resulted in a larger plasma AUC(Nap):AUC(Nap-G) ratio for the R-glucuronide. There was, however, no marked difference in the apparent clearance of the R- and S-diastereomers. Administration of phenylmethylsulfonylfluoride had no significant effect on the disposition of the two diastereomers. In 0.15 M phosphate buffer (ph 7.4) at 37 degree C, the fastest degradation process for both diastereomers in vitro was acyl migration. Our results show that R-naproxen glucuronide is more labile than S-naproxen glucuronide in vivo and in vitro, and suggest that hydrolysis, rather than biliary excretion, is the major process leading to elimination of R-naproxen glucuronide in vivo in the rat. These results demonstrate that the rat may in certain situations be an inadequate model for studying the disposition of acyl glucuronides and that the metabolic disposition, and possibly toxicities, of diastereomeric metabolites of chiral drugs can be quite different even when the individual diastereomers have similar apparent clearances.

Animals↗
PubMed1998

[Management of postoperative pain in stomatology with ibuprofen L-arginine and naproxen].

BACKGROUND: The aim of this prospective, randomized study is to compare the efficacy and safety of ibuprofen L-arginine and naproxen in the treatment of postoperative dental pain. METHODS: Seventy patients undergoing removal of impacted third molars were randomly allocated to receive 4 hours after surgery a single oral dose of either ibuprofen L-arginine 400 mg or naproxen 550 mg. Ten patients dropped out from the study because they took the study drug before the allowed time. Using a self-rating record, patients rated their pain and its relief for 1 hour after the drug administration. Remedication, if needed, and mean time of remedication were also recorded. RESULTS: A statistically significant reduction in pain scores with respect to the baseline values was recorded 5 minutes and 15 minutes after the drug administration in the ibuprofen L-arginine and in the naproxen-treated group, respectively. The summed pain intensity difference (SPID) over 60 minutes resulted significantly higher in the ibuprofen L-arginine than in the naproxen-treated group. A complete abolition of pain 60 minutes after medication was obtained in 12/28 patients (42.9%) in the ibuprofen L-arginine and in 5/32 patients (15.6%) in the naproxen-treated group, respectively (p = 0.04). Number of patients requiring remedication, mean time of remedication and drug related adverse effects did not significantly differ in the two treatment group. CONCLUSIONS: Global evaluation of the drugs by the patients showed ibuprofen more effective drug than naproxen.

Adolescent↗
PubMed1998

Bioavailability, food effect and tolerability of S-naproxen betainate sodium salt monohydrate in steady state.

S-Naproxen betainate sodium salt monohydrate (naproxen-beta Na, CAS 104124-26-7, Aprenin) in 550 mg capsules (corresponding to 327 mg of naproxen) was administered to 24 healthy volunteers (12 males and 12 females) b.i.d. to steady state in order to check its bioavailability, food interaction and tolerability. Plasma concentrations of naproxen were measured by a well validated HPLC method with fluorimetric detection as a morning pre-dose on days 1 to 6 and in timed samples in three different situations, as follows: a) after the morning dose on day 7 in a fasting status, b) after the evening dose and dinner on day 7 and c) after the morning dose of day 8, taken after a high-fat content breakfast. Pharmacokinetic parameters were evaluated from plasma concentrations by non-compartmental analysis to describe the above three situations. The steady state was reached early, namely by the second day of treatment. The extent of absorption did not differ in the three situations tested, whereas the rate of absorption was fastest in fasting conditions, lowest with the evening dose and intermediate after the high-fat content breakfast. The slow absorption rate of the evening dose was attributed to a circadian rhythm and should allow therapeutically active levels early in the morning, when arthritis pain is particularly tedious. In the three situations explored Cmax, Cmin and AUC were associated with CV % values ranging from 11.7 to 17.2%, which are very low and rare in pharmacokinetic trials. This low variability should allow an accurate estimate of the therapeutic effect expected. Tolerability was checked by objective and subjective symptoms, including vital signs, blood/urine biochemical parameters and occult blood in stools, and proved to be very good. From the comparison of these data with those previously published by other authors who have administered 500 mg of naproxen b.i.d., pre-dose concentrations in a steady state proved to be similar, despite the different doses administered, whereas Cmax and AUC obtained in this study were marginally lower. The kind of food interaction was the same as previously described in literature with naproxen.

Adolescent↗
PubMed2002

Comparison of low-dose rofecoxib versus 1000 mg naproxen in patients with osteoarthritis. Results of two randomized treatment trials of six weeks duration.

OBJECTIVE: To compare the efficacy and safety of rofecoxib 12.5 mg once daily to naproxen 500 mg twice daily in patients > or = 40 years of age with knee or hip osteoarthritis (OA). METHOD: Two identical 6-week, randomized, double-blind studies were conducted (1 in Africa, Australia, Europe, Canada, Mexico, & South America; 1 in Asia). Primary endpoints were pain walking on a flat surface, patient global assessment of response to therapy, and investigator global assessment of disease status. RESULTS: Overall, 944 patients participated. For all efficacy endpoints, treatment effects for rofecoxib and naproxen were comparable and seen at the first measures of efficacy. Both compounds were generally well-tolerated, with an improved gastrointestinal safety profile for rofecoxib versus naproxen. CONCLUSIONS In these studies, rofecoxib 12.5 mg once daily (the lowest indicated dose) and naproxen 500 mg twice daily showed similar treatment effects in OA patients. Rofecoxib and naproxen were generally well tolerated.

Aged↗
PubMed2003

Effect of selective cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute myocardial infarction in the elderly.

BACKGROUND: Recent debate has emerged regarding the cardiovascular safety of selective cyclooxygenase 2 inhibitors and the possible cardioprotective effect of naproxen sodium. We compared the rates of acute myocardial infarction (AMI) among elderly patients dispensed selective cyclooxygenase 2 inhibitors, naproxen, and nonselective nonnaproxen nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: We conducted a population-based retrospective cohort study using administrative health care data from Ontario, Canada, from April 1, 1998, to March 31, 2001. We identified NSAID-naive cohorts of subjects aged 66 years and older in whom treatment was initiated with celecoxib (n = 15 271), rofecoxib (n = 12 156), naproxen (n = 5669), and nonnaproxen nonselective NSAIDs (n = 33 868), along with a randomly selected control cohort not exposed to NSAIDs (n = 100 000). Multivariate Cox proportional hazards models were used to compare AMI rates between study drug groups while controlling for potential confounders. RESULTS: Relative to control subjects, the multivariate model showed no significant differences in AMI risk for new users of celecoxib (adjusted rate ratio [aRR], 0.9; 95% confidence interval [CI], 0.7-1.2), rofecoxib (aRR, 1.0; 95% CI, 0.8-1.4), naproxen (aRR, 1.0; 95% CI, 0.6-1.7), or nonnaproxen nonselective NSAIDs (aRR, 1.2; 95% CI, 0.9-1.4). CONCLUSIONS: The findings of this observational study suggest no increase in the short-term risk of AMI among users of selective cyclooxygenase 2 inhibitors as commonly used in clinical practice. Furthermore, the findings do not support a short-term reduced risk of AMI with naproxen.

Aged↗
PubMed2002

NO-donors (VII [1]): synthesis and cyclooxygenase inhibitory properties of N-and S-nitrooxypivaloyl-cysteine derivatives of naproxen -- a novel type of NO-NSAID.

Nitric oxide (NO)has been reported to subserve many of the same mucosal protection mechanisms as prostaglandins and is sufficient for acute gastroprotection and ulcer healing. In fact, NO-donating NSAID hybrid compounds such as the nitrooxybutyl ester of naproxen show reduced ulcerogenic activity while maintaining anti-inflammatory activity. We introduce two prototypes of novel triple-hybrid compounds consisting of cysteine which is known to enhance the activity of organic nitrates and to reduce nitrate tolerance, an NSAID (naproxen), and an organic nitrate (nitrooxypivaloic acid). L-Cysteine ethyl ester first was N-acylated in a CH(2)Cl(2)/H(2)O twophase system using the acid chlorides of naproxen or nitrooxypivaloic acid, respectively, and sodium acetate, or alternatively using the DCC-activated nitrooxy acid in absolute CH(2)Cl(2). The N-acylated intermediates were subsequently S-acylated using the acid chlorides or alternatively the carbonyldiimidazole (CDI)-activated acids again. The two naproxen-cysteine-nitrate hybrid prodrugs were screened in vitro for their cyclooxygenase inhibitory properties relative to naproxen. In this screening the N-nitrooxyacylcysteine derivative was found to be inactive in the concentration range of 0.1-10 micromol/L against both COX-1 and COX-2, while the S-nitrooxyacylcysteine derivative had only weak activity against COX-1.

Animals↗