Human pharmacology of naproxen sodium

We compared the variability in degree and recovery from steady-state inhibition of cyclooxygenase (COX)-1 and COX-2 ex vivo and in vivo and platelet aggregation by naproxen sodium at 220 versus 440 mg b.i.d. and low-dose aspirin in healthy subjects. Six healthy subjects received consecutively naproxen sodium (220 and 440 mg b.i.d.) and aspirin (100 mg daily) for 6 days, separated by washout periods of 2 weeks. COX-1 and COX-2 inhibition was determined using ex vivo and in vivo indices of enzymatic activity: 1) the measurement of serum thromboxane (TX)B(2) levels and whole-blood lipopolysaccharide-stimulated prostaglandin (PG)E(2) levels, markers of COX-1 in platelets and COX-2 in monocytes, respectively; 2) the measurement of urinary 11-dehydro-TXB(2) and 2,3-dinor-6-keto-PGF(1alpha) levels, markers of systemic TXA(2) biosynthesis (mostly COX-1-derived) and prostacyclin biosynthesis (mostly COX-2-derived), respectively. Arachidonic acid (AA)-induced platelet aggregation was also studied. The maximal inhibition of platelet COX-1 (95.9 +/- 5.1 and 99.2 +/- 0.4%) and AA-induced platelet aggregation (92 +/- 3.5 and 93.7 +/- 1.5%) obtained at 2 h after dosing with naproxen sodium at 220 and 440 mg b.i.d., respectively, was indistinguishable from aspirin, but at 12 and 24 h after dosing, we detected marked variability, which was higher with naproxen sodium at 220 mg than at 440 mg b.i.d. Assessment of the ratio of inhibition of urinary 11-dehydro-TXB(2) versus 2,3-dinor-6-keto-PGF(1alpha) showed that the treatments caused a more profound inhibition of TXA(2) than prostacyclin biosynthesis in vivo throughout dosing interval. In conclusion, neither of the two naproxen doses mimed the persistent and complete inhibition of platelet COX-1 activity obtained by aspirin, but marked heterogeneity was mitigated by the higher dose of the drug.     

萘普生缓释片处方工艺因素对体外溶出的影响

背景:药物以缓释片剂形式存在,可减少用药次数,延长释药时间,有利于其治疗效应的发挥.目的:制备萘普生缓释片,考察其处方工艺因素对体外溶出的影响.设计、时间及地点:以重复测量设计在2005-09于顺德职业技术学院实验室完成实验.材料:萘普生、Ⅱ号丙烯酸树脂、羟丙基甲基纤维素(Hydroxypropyl Methyl Cellulose, HPMC)和硬脂酸由广州市新港化工有限公司提供,乙醇为分析纯.方法:经单因素考察,采用正交试验设计,筛选萘普生缓释片处方(萘普生250g,HPMC(K4M)12.5g,乙醇适量,硬脂酸镁1.2g).以不同材料(硬脂酸、HPMC、20%丙烯酸树脂Il、聚维酮K30),不同黏度规格的HPMC(K4M,K15M,K100M),不同硬度的HPMC(2,4,6kg),在相同粒度和相同压力下压片.主要观察指标:不同材料、不同黏度规格的HPMC、不同硬度对释放度的影响.测定并比较萘普生缓释片的释药速度及释放效果.结果:①材料为HPMC的缓释片较符合缓释片标准.用黏度规格为K4M所制缓释片8h释放度符合缓释片标准.硬度为2,4,6Kg,压力越大,释放越慢.②所制备的萘普生缓释片在12h内呈现良好的零级释放特征.结论:该处方制出的萘普生缓释片具有理想的缓释效果.     

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。     

头孢哌酮钠促溶方法对比研究

目的 探讨头孢哌酮钠的促溶方法。方法 采用36支(1g/支)注射用头孢哌酮钠进行试验，将每支分为三等分后分别纳入加温促溶组、机械振荡组、碳酸氢钠促溶组进行溶解试验，比较各组溶解情况。结果 从溶解速度来看，机械振荡组最快，碳酸氢钠促溶组其次，加温促溶组最慢，其中仅碳酸氢钠促溶组未出现再凝。结论 碳酸氢钠促溶是可行的方法。     

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.     

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.     

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.     

新型抗精神病药物对康复期精神分裂症患者认知功能的影响

目的 探讨康复期精神分裂症患者认知功能损害特点及新型非典型抗精神病药物对认知功能的影响.方法 对50例康复期精神分裂症患者常规应用新型非典型抗精神病药物治疗,观察8周.于治疗前及治疗8周末采用华文认知能力量表评定患者的认知功能状况,采用阳性与阴性症状量表评定精神症状,对评定结果 进行对比分析.结果 入组患者常规应用新型抗精神病药物治疗8周末,阳性与阴性症状量表减分率达(51.5±20.3)%;华文认知能力量表工作记忆、学习能力、推理能力、加工速度、空间/计算维度分和言语智商、操作智商、总智商评分均较治疗前有显著提高(P＜0.01).治疗前后华文认知能力量表总智商评分差值与阳性与阴性症状量表总分及阳性症状因子分差值呈显著正相关(P＜0.01),而与阴性症状及精神病理因子分差值无显著相关性(P＞0.05).结论 康复期精神分裂症患者均存在不同程度的认知功能损害,新型抗精神病药物在改善患者各种精神症状的同时,还能显著改善患者的认知功能.     

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.     

Upper gastrointestinal safety evaluation of parecoxib sodium, a new parenteral cyclooxygenase-2-specific inhibitor, compared with ketorolac, naproxen, and placebo

BACKGROUND: Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of ulcers and upper gastrointestinal (GI) ulcer complications, which has been attributed to the inhibition of cyclooxygenase-1. These risks are usually increased in elderly populations. Parecoxib sodium is an injectable prodrug of the cyclooxygenase-2-specific inhibitor valdecoxib that has exhibited analgesic activity in previous trials. OBJECTIVE: The purpose of this study was to compare the GI safety and tolerability profile of parecoxib sodium with that of ketorolac, naproxen, and placebo in a 7-day endoscopic trial in elderly subjects. METHODS: This was a randomized, double-blind, double-dummy, placebo-controlled, parallel-group study. After a normal baseline endoscopy, healthy elderly subjects aged 66 to 75 years were randomized to receive i.v. parecoxib sodium (10 mg BID), oral naproxen (500 mg BID), or placebo for 7 days, or placebo for 2 days followed by i.v. ketorolac (15 mg QID) for 5 days. Endoscopy was performed again after 7 days. RESULTS: Among the first 17 subjects enrolled, ulcers were observed in all treatment groups except the parecoxib sodium group (ketorolac, 4/4 subjects; naproxen, 2/4 subjects; and placebo, 2/5 subjects). Four subjects in the ketorolac group and 1 subject in the naproxen group had multiple gastric ulcers or combined gastric and duodenal ulcers. Because of the unexpectedly high incidence of gastroduodenal ulcers observed, the study was terminated early and the randomization blind broken. CONCLUSION: These findings suggest that elderly patients may be at risk for GI ulceration even after short-term use of the conventional NSAIDs ketorolac and naproxen.     

医护一体化分组管理对老年前列腺增生患者微波热疗效果的影响

目的 探讨医护一体化分组管理对老年前列腺增生患者微波热疗效果的影响.方法 将108例老年前列腺增生患者按照入院顺序随机分为两组,每组54例.观察住院全程.研究组采用医护一体化分组管理模式,对照组采用常规责任者整体护理模式.比较两组患者的手术时间、术后前列腺体积及并发症状况,发放问卷调查患者满意度.结果 研究组手术时间短于对照组,前列腺体积大于对照组,但差异无显著性(P＞0.05).研究组患者满意度显著高于对照组(P＜0.01),并发症发生率显著低于对照组(P＜o.05).结论 医护一体化分组管理模式可显著提高老年前列腺增生微波热疗患者的满意度,降低术后并发症发生率,缩短手术时间,对提高医疗护理质量具有重要作用.     

Sustained‐release of naproxen sodium from electrospun‐aligned PLLA–PCL scaffolds

Spontaneous tendon healing may result in reduced tissue functionality. In view of this, tissue engineering (TE) emerges as a promising approach in promoting proper tendon regeneration. However, unfavourable post‐surgical adhesion formations restrict adequate tendon healing through the TE approach. Naproxen sodium (NPS), a non‐steroidal anti‐inflammatory drug (NSAID), has been demonstrated to prevent adhesions by inhibiting the inflammatory response. Therefore, in this study, various factors, such as polymer composition, i.e. different poly‐l ‐lactic acid (PLLA):polycaprolactone (PCL) ratios, and percentage of water:hexafluoroisopropanol (HFIP; as co‐solvent) ratios, were investigated to understand how these can influence the release of NPS from electrospun scaffolds. By adjusting the amount of water as the co‐solvent, NPS could be released sustainably for as long as 2 weeks. Scaffold breaking strength was also enhanced with the addition of water as the co‐solvent. This NPS‐loaded scaffold showed no significant cytotoxicity, and L929 murine fibroblasts cultured on the scaffolds were able to proliferate and align along the fibre orientation. These scaffolds with desirable tendon TE characteristics would be promising candidates in achieving better tendon regeneration in vivo. Copyright © 2015 John Wiley & Sons, Ltd.     

Effect of diclofenac and naproxen on gastroduodenal mucosa.

The increases in medan scoresfluence on gastroduodenal mucosa of naproxen, 500 mg/day, and diclofenac, 100 mg/day, for 1 wk was investigated in 14 subjects in a double-blind randomized crossover study. Endoscopic examination of the gastroduodenal mucosa was carried out before and after each drug with regard to gastritis and hemorrhagic and erosive lesions. A 20-cm visual analogue scale was used for grading severity of mucosal changes. Naproxen caused statistically significant increases inmedian scores for all 3 variables, and 10 subjects showed a score increase in at least 1 variable; reaction to diclofenac occurred in only 4 subjects and the changes in median scores were not significant.     

Comparison of the efficacy and safety of nonprescription doses of naproxen and naproxen sodium with ibuprofen,acetaminophen, and placebo in the treatment of primary dysmenorrhea: a pooled analysis of five studies

BACKGROUND: Dysmenorrhea is the most common menstrual complaint in young women, with a prevalence as high as 90%. It is responsible for substantial repeated short-term absenteeism from school and work in young women. Effective treatments are available, including nonsteroidal anti-inflammatory drugs (NSAIDs). In many countries, a variety of NSAIDs have become available as over-the-counter (OTC) drugs. OBJECTIVE: The goal of this study was to compare the efficacy and safety of OTC doses of naproxen (400 mg) and naproxen/naproxen sodium (200/220 mg) with acetaminophen (1000 mg), ibuprofen (200 mg), and placebo in the treatment of primary dysmenorrhea. METHODS: A pooled analysis of 5 trials was performed. Efficacy was assessed by pain relief, relief of other dysmenorrheic symptoms, time to backup medication or remedication, and treatment preference. Tolerability was assessed by recording adverse events (AEs). RESULTS: A total of 443 women were enrolled in the combined studies. Naproxen 400 mg provided greater pain relief than acetaminophen and placebo within 30 minutes of administration (P < 0.01 and P < 0.05, respectively). Furthermore, naproxen 400 mg and 200 mg provided greater pain relief than both acetaminophen (P < 0.01 and P < 0.05, respectively) and ibuprofen (P < 0.001 and P < 0.01, respectively) at 6 hours after administration. Both doses of naproxen had higher scores than placebo for symptom relief and drug preference (all P < 0.001). The AEs and their frequency were similar among the treatment groups. No serious AEs were reported. CONCLUSION: When administered at OTC doses, naproxen was effective in the relief of pain and other symptoms of primary dysmenorrhea and had a good safety profile in the population studied.