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.
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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+info)
Platelet function is inhibited by non-selective non-steroidal anti-inflammatory drugs but not by cyclo-oxygenase-2-selective inhibitors in patients with rheumatoid arthritis.
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BACKGROUND: Interaction with platelet function by non-steroidal anti-inflammatory drugs (NSAIDs) is related to the inhibition of cyclo-oxygenase-1 (COX-1). In patients with rheumatoid arthritis (RA), only one of the COX-2-selective NSAIDs (nabumetone) has been demonstrated to spare platelet function partially. OBJECTIVE: To compare the effects of the COX-2-selective inhibitor, meloxicam, with those of the non-selective NSAID, naproxen, on platelet function and thromboxane levels in RA patients. METHODS: In this randomized, controlled, cross-over trial, 10 RA patients used meloxicam 7.5 mg bid and naproxen 500 mg bid, each during a 2-week period. Washout periods were applied. Before and after each 2-week period of NSAID intake, laboratory studies were performed. RESULTS: Platelet aggregation was significantly less influenced, thromboxane levels were less inhibited (246 vs 117 pg/ml) and bleeding times were less prolonged with meloxicam than with naproxen (3.2 vs 2.3 min). Moreover, the results of all tests during meloxicam exposure were comparable with baseline values. CONCLUSION: In RA patients, meloxicam, a representative of the selective COX-2 inhibitors, does not interfere with platelet function and thromboxane levels, in contrast with naproxen (a non-selective COX inhibitor). (+info)
Topical naproxen sodium for inhibition of miosis during cataract surgery. Prospective, randomized clinical trials.
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PURPOSE: To assess corneal penetration of naproxen sodium and its efficacy in maintaining intraoperative mydriasis during cataract surgery. METHODS: Two double blind studies have been performed comparing the efficacy of naproxen ophthalmic solution to that of placebo or diclofenac in inhibiting pre-operative miosis. Study No. 1 was a placebo-controlled study and involved 194 patients undergoing extracapsular cataract extraction. Study No. 2 was an active-controlled study (vs diclofenac) concerning 214 patients undergoing phacoemulsification. In both studies treatment started the day before surgery. A balanced salt solution containing adrenaline was used in all patients. Pupil size was measured prior to the corneal section and at the end of surgery. An aqueous humor sample was taken immediately before corneal incision in a subset of 20 patients to measure naproxen aqueous concentration. RESULTS: In both studies the pupillary diameter decreased during surgery within each treatment group in a statistically significant manner (P < 0.001). Naproxen was more effective than placebo (P < 0.01) and as effective as diclofenac in controlling pupil diameter regression during cataract. Mean concentration level of naproxen in the aqueous humor was 372.3 ng/ml. CONCLUSIONS: Naproxen sodium ophthalmic solution penetrates the cornea and it is effective in maintaining intraoperative mydriasis. (+info)
A multinational randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis [ISRCTN25142273].
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BACKGROUND: Etoricoxib is a highly selective COX-2 inhibitor which was evaluated for the treatment of rheumatoid arthritis (RA). METHODS: Double-blind, randomized, placebo and active comparator-controlled, 12-week study conducted at 67 sites in 28 countries. Eligible patients were chronic NSAID users who demonstrated a clinical worsening of arthritis upon withdrawal of prestudy NSAIDs. Patients received either placebo, etoricoxib 90 mg once daily, or naproxen 500 mg twice daily (2:2:1 allocation ratio). Primary efficacy measures included direct assessment of arthritis by counts of tender and swollen joints, and patient and investigator global assessments of disease activity. Key secondary measures included the Stanford Health Assessment Questionnaire, patient global assessment of pain, and the percentage of patients who achieved ACR20 responder criteria response (a composite of pain, inflammation, function, and global assessments). Tolerability was assessed by adverse events and routine laboratory evaluations. RESULTS: 1171 patients were screened, 891 patients were randomized (N = 357 for placebo, N = 353 for etoricoxib, and N = 181 for naproxen), and 687 completed 12 weeks of treatment (N = 242 for placebo, N = 294 for etoricoxib, and N = 151 for naproxen). Compared with patients receiving placebo, patients receiving etoricoxib and naproxen showed significant improvements in all efficacy endpoints (p<0.05). Treatment responses were similar between the etoricoxib and naproxen groups for all endpoints. The percentage of patients who achieved ACR20 responder criteria response was 41% in the placebo group, 59% in the etoricoxib group, and 58% in the naproxen group. Etoricoxib and naproxen were both generally well tolerated. CONCLUSIONS: In this study, etoricoxib 90 mg once daily was more effective than placebo and similar in efficacy to naproxen 500 mg twice daily for treating patients with RA over 12 weeks. Etoricoxib 90 mg was generally well tolerated in RA patients. (+info)
Developing an economic rationale for the use of selective COX-2 inhibitors for patients at risk for NSAID gastropathy.
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Arthritis causes considerable patient morbidity and substantial health care resource utilization. One important contributing component to the overall cost burden of this condition is the variety of expenditures attributable to the adverse effects of arthritis therapy. Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are a mainstay of medical treatment for patients with arthritis because of their well-established anti-inflammatory and analgesic effects. Generally well tolerated, traditional NSAIDs nevertheless cause adverse gastrointestinal (GI) effects in a proportion of patients. Because nonselective NSAIDs are so widely used, these GI adverse events cause significant morbidity and mortality, accounting for substantial additional health care expenditures. Data from controlled investigations document the enhanced GI safety of cyclooxygenase (COX)-2-selective inhibitors, or coxibs, when compared with nonselective NSAIDs. As a result of this improved safety profile, patients treated with coxibs use significantly fewer GI-related health care resources (eg, medications, procedures) than patients treated with nonselective NSAIDs. Thus, available clinical and economic data suggest that the use of coxibs has the potential to result in important clinical GI benefits at an acceptable incremental cost for all chronic NSAID users. For individuals who are at an increased risk of developing GI complications attributable to NSAIDs, coxibs are clearly a cost-effective treatment option. (+info)
Efficacy and safety of valdecoxib in treating the signs and symptoms of rheumatoid arthritis: a randomized, controlled comparison with placebo and naproxen.
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OBJECTIVE: To compare the efficacy of the COX-2 specific inhibitor valdecoxib with the conventional NSAID naproxen and placebo in treating rheumatoid arthritis (RA). METHODS: This multi-centre, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of valdecoxib 10 mg (n=209), 20 mg (n=212) or 40 mg once daily (q.d.) (n=221) with naproxen 500 mg b.i.d. (n=226) or placebo (n=222), in treating the signs and symptoms of RA. Efficacy was assessed by the number of patients responding to treatment according to the American College of Rheumatology-Responder Index (ACR-20). RESULTS: ACR-20 response was recorded for all randomized patients who received a single dose of study medication (above). Valdecoxib, at all administered doses, produced significant improvements in the ACR-20 Responder Index at weeks 2, 6 and 12 compared with placebo (P+info)
Naproxen ion-selective electrode and its application to pharmaceutical analysis.
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An ion-selective membrane electrode was prepared based on ion-pair complex of naproxen with methyltrioctylammonium. Its basic analytical parameters such as: slope characteristics, measuring range, detection limit, response time, life time were determined. The electrode showed Nernstian response from the 10(-1) to 10(-4) mol l(-1) concentration range and 5.5-8.5 pH range, low limit of detection 5 x 10(-5) mol l(-1) and short response time--20s. Selectivity was good over a number of organic and inorganic anions. The electrode was applied for the determination of naproxen tablets in aqueous solutions by the calibration curve method and standard addition method. (+info)
Activation of CYP2C9-mediated metabolism by a series of dapsone analogs: kinetics and structural requirements.
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Cytochrome P450 2C9-mediated metabolism has been shown to be activated in the presence of the effector dapsone. However, it has yet to be established what effector structural features are necessary to activate CYP2C9 activity. To address this question, kinetic studies were conducted with nine analogs of dapsone containing various functional properties (three sulfone compounds, three carbonyl compounds, and three sulfonamide compounds), to examine the functional groups important for enzyme activation by the effector (dapsone). Results show that phenylsulfone (dapsone without the para-amino groups) activates flurbiprofen 4'-hydroxylation comparable to dapsone but inhibits naproxen demethylation. Meanwhile, p-tolylsulfone had little effect on flurbiprofen metabolism, but activated naproxen demethylation, albeit only at high concentrations. These substrate-dependent differences in effect suggest that naproxen has a different binding orientation compared with flurbiprofen. Perhaps most interesting is that replacement of only one amino group from dapsone with a nitro group (4-(4-nitrophenylsulfonyl)-aniline) resulted in substantial inhibition of flurbiprofen 4'-hydroxylation, suggesting that electronic effects may influence activation of this substrate. Other analogs either had minor or no effect on CYP2C9-mediated metabolism. Overall, it is apparent from these studies that a sulfone group in direct association with two benzene rings with para-electron-donating groups represents the most efficient activator of CYP2C9. However, the effects of these analogs appear to be concentration- and substrate-dependent, further complicating the prediction of these types of in vitro interactions. (+info)