应用萘普生钠治疗类风湿性关节炎

本文报告了萘普生钠对34例类风湿性关节炎的疗效,按美国风湿病学会标准选择病例,做双盲试验,有效率为94％,副作用主要为消化道反应。     

Sumatriptan and naproxen sodium for the acute treatment of migraine

OBJECTIVE: To evaluate the efficacy and tolerability of treatment with a combination of sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg administered concurrently in the acute treatment of migraine. BACKGROUND: The pathogenesis of migraine involves multiple peripheral and central neural mechanisms that individually have been successful targets for acute (abortive) and preventive treatment. This suggests that multi-mechanism therapy, which acts on multiple target sites, may confer improved efficacy and symptom relief for patients with migraine. DESIGN AND METHODS: This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, four-arm study. Participants (n = 972) treated a single moderate or severe migraine attack with placebo, naproxen sodium 500 mg, sumatriptan 50 mg, or a combination of sumatriptan 50 mg and naproxen sodium 500 mg. In the latter two treatment arms, the sumatriptan tablets were encapsulated in order to achieve blinding of the study. RESULTS: In the sumatriptan plus naproxen sodium group, 46% of subjects achieved 24-hour pain relief response (primary endpoint), which was significantly more effective than sumatriptan alone (29%), naproxen sodium alone (25%), or placebo (17%) (P < .001). Two-hour headache response also significantly favored the sumatriptan 50 mg plus naproxen sodium 500 mg therapy (65%) versus sumatriptan (49%), naproxen sodium (46%), or placebo (27%) (P < .001). A similar pattern of between-group differences was observed for 2-hour pain-free response and sustained pain-free response (P < .001). The incidence of headache recurrence up to 24 hours after treatment was lowest in the sumatriptan plus naproxen sodium group (29%) versus sumatriptan alone (41%; P = .048), versus naproxen sodium alone (47%; P= .0035), and versus placebo (38%; P= .08). The incidences of the associated symptoms of migraine were significantly lower at 2 hours following sumatriptan 50 mg plus naproxen sodium 500 mg treatment versus placebo (P < .001). The frequencies and types of adverse events reported did not differ between treatment groups, with dizziness and somnolence being the most common. CONCLUSIONS: This is among the first prospective studies to demonstrate that multi-mechanism acute therapy for migraine, combining a triptan and an analgesic, is well tolerated and offers improved clinical benefits over monotherapy with these selected standard antimigraine treatments. Specifically, sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg resulted in significantly superior pain relief as compared to monotherapy with either sumatriptan 50 mg (encapsulated) or naproxen sodium 500 mg for the acute treatment of migraine. Because encapsulation of the sumatriptan for blinding purposes may have altered its pharmacokinetic profile and thereby decreased the efficacy responses, additional studies are warranted that do not involve encapsulation of the active treatments and assess the true onset of action of multi-mechanism therapy in migraine. This study did show that the combination of sumatriptan and naproxen sodium was well tolerated and that there was no significant increase in the incidence of adverse events compared to monotherapy.     

Human pharmacology of the methamphetamine stereoisomers

OBJECTIVE: To help predict the consequences of precursor regulation, we compared the pharmacokinetics and pharmacodynamics of the methamphetamine (INN, metamfetamine) stereoisomers. METHODS: In this study 12 methamphetamine abusers received intravenous d-methamphetamine (0.25 and 0.5 mg/kg), l-methamphetamine (0.25 and 0.5 mg/kg), racemic methamphetamine (0.5 mg/kg), or placebo with the use of a 6-session, double-blind, placebo-controlled, balanced crossover design. Pharmacokinetic measures (including area under the plasma concentration-time curve [AUC], elimination half-life, systemic clearance, apparent volume of distribution during the elimination phase, and apparent bioavailability) and pharmacodynamic measures (including heart rate, blood pressure, respiratory rate, and visual analog scale ratings for "intoxication," "good drug effect," and "drug liking") were obtained. RESULTS: Pharmacokinetic parameters for the individual enantiomers given separately were similar, with dose-proportional increases in AUC and maximum plasma concentration. After racemate administration, the AUC for d-methamphetamine was 30% smaller than that for l-methamphetamine (P = .0085). The elimination half-lives were longer for l-methamphetamine (13.3-15.0 hours) than for d-methamphetamine (10.2-10.7 hours) (P < .0001). Compared with placebo, d-methamphetamine (0.25 mg/kg, 0.5 mg/kg, and racemic) increased the heart rate (P < .0001), blood pressure (P < .0001), and respiratory rate (P < .05), and this increase lasted for 6 hours. The peak heart rate changes after racemic methamphetamine and 0.5 mg/kg d- and l-methamphetamine were similar (18.7 +/- 23.4 beats/min, 13.5 +/- 18.5 beats/min, and 10.7 +/- 10.2 beats/min, respectively), but racemic methamphetamine and 0.5 mg/kg d-methamphetamine increased systolic blood pressure more than 0.5 mg/kg l-methamphetamine (33.4 +/- 17.8 beats/min and 34.5 +/- 18.9 beats/min, respectively, versus 19.5 +/- 11.3 beats/min; P < .01). l-Methamphetamine, 0.5 mg/kg, was psychoactive, producing peak intoxication (46.0 +/- 35.3 versus 30.3 +/- 24.9) and drug liking (47.7 +/- 35.1 versus 28.6 +/- 24.8) ratings similar to 0.5 mg/kg d-methamphetamine, but the effects of l-methamphetamine dissipated more quickly (approximately 3 hours versus 6 hours). The effects of 0.25 mg/kg l-methamphetamine were similar to those of placebo. Racemic methamphetamine was similar to d-methamphetamine with regard to most pharmacodynamic measures. CONCLUSION: The pharmacokinetics of the methamphetamine enantiomers are similar, but there are substantial pharmacodynamic differences between the isomers. At high doses, l-methamphetamine intoxication is similar to that of d-methamphetamine, but the psychodynamic effects are shorter-lived and less desired by abusers. Racemic and d-methamphetamine have similar effects and would be expected to have comparable abuse liabilities.     

Evaluation of the quality of four Mexican drug products containing sodium naproxen

Background:  There is currently a lot of concern about the quality and therapeutic effectiveness of Mexican pharmaceutical products, and considerable price differences between alternative products containing the same active principle. Objective:  To establish whether four Mexican drug products, a high price and three lower‐cost branded drug products containing sodium naproxen (550 mg immediate release tablets) have equivalent, and consistent pharmaceutical qualities. Methods:  The four products were acquired in Mexico city. Assay for sodium naproxen, content uniformity, disintegration time and dissolution tests were performed according to USP procedures. Drug dissolution profiles were compared using a similarity factor (f₂). Results and discussion:  All of the tested products met pharmacopeial quality standards with respect to their active pharmaceutical content and a released drug percentage >70% in 45 min. Lot‐to‐lot lack of similarity between drug dissolution profiles was observed for two of the products tested. Conclusion:  There was no significant differences in the quality of the pharmaceutical products tested when judged by the USP pharmaceutical quality standards. However, some differences were observed in the dissolution profiles of the brands tested. Whether these differences are clinically meaningful requires in vivo bioequivalence studies.     

Influences of novel microwave drying on dissolution of new formulated naproxen sodium

Drying of a pharmaceutical composition is an important step during its processing, which can affect its quality attributes including its texture, dispersion of the drug within the formulation, drug dissolution kinetics and eventually the drug''s efficacy. This study presents the influence of varying drying techniques on the textural properties of the wet granulated formulation consisting of the drug naproxen sodium (NapSod) during the drying process. A new pharmaceutical formulation consisting of the NapSod drug was prepared by wet granulation and dried by novel microwave drying (MW), freeze drying (FD), vacuum drying (VD), and convective drying (CD) techniques before being processed in the form of tablets. The dissolution rate of NapSod from the tablet was measured in gastric (pH = 1.3) and intestinal fluid (pH = 6.8) mediums. The drug release was found to be influenced by the specific surface area, size distribution and the crystalline structure of dried particles, which were found to vary with the type of drying technique used as confirmed by the results of XRD, FTIR, SEM and particle size analyses. This study shows that using microwave technique to dry pharmaceutical granules containing a polar drug, such as NapSod, is an efficient and economical process, which can maintain the drug release at an appropriate rate to realize its desired pharmaceutical effect.

Novel microwave mediated drying of naproxen sodium has been shown as an efficient drying technique as well as exhibiting a critical role in improving the dissolution kinetics.     

Human pharmacology and abuse potential of nalmefene

Nalmefene hydrochloride was administered to six male volunteers with histories of opiate abuse using a double-blind, randomized, Latin square design to determine if it produced typical morphine-like effects. A comparison of physiologic and subject- and observer-reported effects was made between morphine, 15 and 30 mg given intramuscularly; nalmefene, 25, 50, and 100 mg given orally; and placebo. Drowsiness or sleepiness was the most common drug effect reported after the administration of each treatment. Only morphine produced miosis and increased subject-reported euphoria and "drug liking." Neither drug increased Addiction Research Inventory subscale scores measuring dysphoria or sedation or produced changes on the Profile of Mood States questionnaire. Adverse effects reported only after the administration of nalmefene included agitation/irritability and muscle tension; these did not appear to be dose related. The data indicated that nalmefene did not produce typical morphine-like effects and has no apparent abuse potential.     

Human pharmacology and abuse potential of meptazinol

Meptazinol was assessed in nine opioid abusers according to a double-blind, randomized, crossover design to determine if it produced typical morphine effects. A comparison of physiologic and subjective effects was made between morphine, 7.5, 15, and 30 mg, meptazinol, 70, 140, and 280 mg, and placebo. Both drugs constricted pupils. Meptazinol, 140 and 280 mg, decreased body temperature. Valid relative potency estimates of morphine to meptazinol were obtained for self-reported liking, opiate symptoms, and pupillary constriction. Meptazinol did not increase euphoria or sedation scale scores but did increase dysphoria scale scores. In the therapeutic dose range, meptazinol produced miosis, morphine-like identification and symptoms, limited liking, and some dysphoria. Dysphoria predominated at the 280 mg dose of meptazinol. From these data, it is concluded that meptazinol is not a typical morphine-like drug and has limited abuse potential.     

Pain relief after arthroscopy: naproxen sodium compared to propoxyphene napsylate with acetaminophen

We compared naproxen sodium (550 mg) and propoxyphene napsylate with acetaminophen (PN/A, 100 mg with 650 mg) for pain relief after arthroscopy or arthroscopic meniscectomy. Fifty-two patients entered this multicenter, double-blind, randomized, parallel trial. In each drug group, pain intensity values dropped consistently throughout this six-hour study from mean baseline levels of approximately 55 on a scale of 0 to 100. Pain intensity values were lower at each hour in the naproxen sodium than in the PN/A group and significantly lower at hour 1 (P = .008). Pain intensity differences (PID, reflecting change from baseline) mirrored this trend: greater mean PIDs were seen in the naproxen sodium group at each hour, and this difference between drug groups was statistically significant at hour 1 (P = .017). One patient in the naproxen sodium group and seven patients using PN/A took a second dose within the six hours. Patients in each drug group reported five complaints.     

The comparative efficacy of naproxen sodium and pirprofen in the treatment of post-operative pain

A randomized, single-blind, parallel study involving 100 adults was performed to compare the efficacy and safety of naproxen sodium with that of pirprofen in the treatment of moderate to severe pain after orthopaedic surgery. Fifty patients received 550 mg of naproxen sodium initially and 275 mg every 6 h thereafter, and 50 received 400 mg of pirprofen every 8 h until either their pain was completely relieved or the 3-day trial ended. Patients who required additional analgesia were given 500 mg of paracetamol 2 h after administration of the test medication. Both medications significantly relieved post-operative pain, and there were no statistically significant differences in efficacy between the groups. Six patients receiving naproxen sodium and two patients receiving pirprofen withdrew from the study because of lack of efficacy. Thirteen patients receiving naproxen sodium recorded 17 adverse events and 13 patients receiving pirprofen recorded 20 adverse events, again with no statistically significant differences between groups. Six patients in each group withdrew from the study because of these adverse events. Naproxen sodium and pirprofen were equally safe and effective in relieving post-operative pain following musculoskeletal surgery.     

Acute migraine attack therapy: comparison of naproxen sodium and an ergotamine tartrate compound

The efficacy of safety of naproxen sodium and ergotamine tartrate were compared for the treatment of acute migraine attack in a randomized, parallel trial with 114 participating patients. At the start of symptoms, patients took either three tablets of naproxen sodium (275 mg each) or one of an ergotamine combination (containing 2 mg ergotamine tartrate, 91.5 mg caffeine, and 50 mg cyclizine chlorhydrate). Patients were followed for three months or until six attacks were monitored, whichever came first. Both medications substantially shortened the duration of migraine attacks and reduced the severity of symptoms. When the test medications were taken within 2 h of onset of attack, naproxen sodium was statistically significantly more effective than the ergotamine combination in reducing the severity of headache pain, nausea, and lightheadedness. The ergotamine combination was associated with significantly more vomiting, need for rescue medication, and side effects than was naproxen sodium. Four patients required discontinuation of the ergotamine combination and one of naproxen sodium. Both patients and investigators rated tolerance for naproxen sodium as superior to tolerance for the ergotamine combination. Naproxen sodium seems to be an effective and safe treatment for migraine attacks.     

Long-term evaluation of sumatriptan and naproxen sodium for the acute treatment of migraine in adolescents

Objectives.— To evaluate the long‐term safety, tolerability, effectiveness, impact on quality of life, and medication satisfaction of sumatriptan/naproxen sodium in the acute treatment of migraine headache in adolescents. Methods.— This 12‐month, multicenter, open‐label, safety study was conducted in adolescents (aged 12‐17 years) with an average of 2‐8 migraines/month typically lasting >2 hours untreated for >6 months prior to initiation. Subjects were instructed to treat migraines as early as possible and were allowed to rescue 2 hours post dose with a single dose of a naproxen‐containing product, over‐the‐counter pain reliever, or anti‐emetics. Subjects were advised not to take a second tablet of sumatriptan/naproxen sodium without at least a 24‐hour headache‐free period. Safety evaluations included adverse events, laboratory tests, and vital signs and electrocardiogram evaluation. Other evaluations included freedom from pain, quality of life, and medication satisfaction. Results.— Of the 656 subjects enrolled, 622 (95%) treated at least 1 migraine with sumatriptan/naproxen sodium, of which 435 (70%) and 363 (58%) completed 6 and 12 months of the study, respectively. Overall, there were 12,927 exposures to sumatriptan/naproxen sodium: on average 2.5 tablets were taken per month per subject. The most common treatment‐related adverse events were nausea (7%), dizziness (3%), muscle tightness (3%), and chest discomfort (3%). There were no deaths; 4 subjects had 5 serious adverse events (suicide attempt, hemolytic anemia and syncope, suicidal ideation, spontaneous abortion) unrelated to sumatriptan/naproxen sodium and resolved without sequelae. Seven percent of subjects discontinued participation in the study because of an adverse event; 5% of subjects discontinued due to lack of efficacy. Overall, 42% of the migraine attacks were pain‐free within 2 hours of treatment with sumatriptan/naproxen sodium, subjects reported improvements from baseline in 2 of 3 quality of life domains over time, and were generally satisfied with the efficacy and overall treatment at the end of the study. Conclusion.— In adolescent migraineurs, after up to 12 months and over 12,000 exposures to sumatriptan/naproxen sodium, there were no new or clinically significant findings in the safety parameters, including the frequency and nature of adverse events, as compared to the individual components or to the adverse event profile in adults. In addition, sumatriptan/naproxen sodium provided freedom from pain over time, improvements in quality of life and medication satisfaction.     

Pathophysiology and pharmacology of the cardiac "late sodium current."

The "late sodium current" (I(NaL)) is a sustained component of the fast Na(+) current of cardiac myocytes and neurons. As recently appreciated, common neurological and cardiac conditions are associated with abnormal I(NaL) enhancement, which may contribute to the pathogenesis of both electrical and contractile dysfunction. For this reason, I(NaL) has become an appealing pharmacological target, with a potentially broad range of therapeutic indications. The recent approval by the FDA of an I(NaL) blocker (ranolazine) for clinical use justifies the increased interest in I(NaL) as a pathogenic mechanism and the rapid evolution of the information concerning it. The review focuses on cardiac aspects of I(NaL) enhancement; it deals with the origin of I(NaL), with its pathophysiological role and with the consequences of its pharmacological modulation. Both basic aspects and clinical evidence are discussed.