尼美舒利和萘普生治疗骨关节炎的临床试验

目的：比较尼美舒利和萘普生治疗骨关节炎的疗效和安全性。方法：采用随机、双盲或单盲、多中心、对照研究方法。尼美舒利１００例（男性４１例，女性５９例，年龄５４±ｓ１０ａ），萘普生６８例（男性２９例，女性３９例，年龄５３±１２ａ）。尼美舒利口服１００ｍｇ，ｂｉｄ；萘普生口服２５０ｍｇ，ｂｉｄ，疗程２ｗｋ。结果：尼美舒利的总有效率为８３％，萘普生的总有效率为７５％（Ｐ＜０．０５）。不良反应发生率分别为２３％和３２％（Ｐ＞０．０５），以胃肠反应为主。结论：尼美舒利对骨关节炎治疗作用优于萘普生，不良反应发生率与萘普生相近。     

Use of a novel non-steroidal anti-inflammatory drug, nimesulide, in the treatment of abacterial prostatovesiculitis

Summary. Nimesulide, a novel non-steroidal anti-inflammatory drug, was used in cases of abacterial prostato-vesiculitis. Thirty patients with a mean age of 33.7 years (range 18–58) were studied. Nimesulide was administered orally 100 mg b.i.d. for three cycles of 10 d each. Dysuric symptoms, semen analysis, and transrectal ultrasound were examined during the study. The concentration-time curves of nimesulide (NIM) and its metabolite, hydroxynimesulide (OH-NIM) in seminal fluid were also evaluated after single oral administration (100 mg) using an HPLC technique. Following administration of the drug, the Cmax was reached in seminal fluid at the second hour for NIM (with a mean value ± SD of 0.58 ± 0.13 μg ml⁻¹) and at the fourth hour for OH-NIM (2.98 ± 0.38 μg ml⁻¹). Maximal seminal fluid concentrations compared to blood plasma levels were observed at the fourth hour for both substances (31.73 ± 2.34% for NIM; 31.87 ± 8.66% for OH-NIM.
Dysurie symptoms were relieved in 20 (66%) patients. A clear amelioration of inflammatory signs were observed at transrectal ultrasound evaluation in 16 (54%) patients. No statistically significant changes of sperm count and motility in the whole sample were observed, while a significant reduction in the number of abnormal forms occurred. From these results, nimesulide appears to be an effective anti-inflammatory drug with a good diffusion into the genital apparatus and low side-effects.     

The effect of nimesulide versus placebo on hemostasis in healthy volunteers

Objective: The primary objective was to evaluate the effect of 7 days treatment with nimesulide on bleeding time. Blood coagulation, von Willebrand factor and platelet aggregation ex vivo were investigated as a secondary objective. Method: A randomised, double-blind, placebo-controlled, parallel group, single centre study performed on 20 healthy male volunteers who received either placebo or nimesulide 100 mg twice daily for 7 days. Bleeding time, platelet count and platelet aggregation, thromboplastin time (prothrombin time), activated partial thromboplastin time, fibrinogen, Factor VIII:C, vWF:Ag, vWF:RCof and platelet-rich plasma aggregation following stimulation with adenosine 5′-diphosphate, collagen, arachidonic acid, ristocetin, thrombin and thrombin receptor-activating peptide were measured at baseline (day 0), and then 3 h after the first (day 1) and last (day 7) treatment. Results: The bleeding times for all subjects remained within the normal range throughout the study period, with no significant differences between the two treatment groups. There were no significant changes from baseline in platelet aggregation studies or in any of the other haemostasis tests, with no significant differences between the two groups. No clinically significant adverse events were reported or observed. Conclusions: Daily administration of 200 mg nimesulide for 7 days neither prolongs bleeding time nor modifies any of the other haemostasis variables measured. The lack of interactions with important haemostatic mechanisms suggests that nimesulide may also be used in patients with bleeding problems. This expectation has still to be confirmed by clinical experience. Received: 6 October 1997 / Accepted in revised form: 5 March 1998     

Methoxybenzamide derivative of nimesulide from anti-fever to anti-cancer: Chemical characterization and cytotoxicity

The repurposing strategy of converting nimesulide from an anti-fever drug to an anti-cancer agent by modifying its main structure targeting HSP27 is gaining great attention these days. The goal of this study focuses on synthesizing a new nimesulide derivative with new ligands that have biological anti-cancer activities in different cancer models using the in-vitro assay. Nimesulide derivative L1 was synthesized, characterized by 1H NMR, 13C NMR, FTIR, melting point, mass spectra, and TGA analysis. A single crystal was diffracted and showed colorless block group P-1. The results revealed that L1 demonstrates potent anti-cancer activity with lung (H292), ovarian (SKOV3), and breast (SKBR3) cancer cell lines in-vitro models with IC₅₀ values below 8.8 µM.     

Rapeseed oil-rich diet alters in vitro menadione and nimesulide hepatic mitochondrial toxicity

Diet-induced changes in the lipid composition of mitochondrial membranes have been shown to influence physiological processes. However, the modulation effect of diet on mitochondrially-active drugs has not yet received the deserved attention. Our hypothesis is that modulation of membrane dynamics by diet impacts drug-effects on liver mitochondrial functioning. In a previous work, we have shown that a diet rich in rapeseed oil altered mitochondrial membrane composition and bioenergetics in Wistar rats. In the present work, we investigated the influence of the modified diet on hepatic mitochondrial activity of two drugs, menadione and nimesulide, and FCCP, a classic protonophore, was used for comparison. The results showed that the effects of menadione and nimesulide were less severe on liver mitochondria for rats fed the modified diet than on rats fed the control diet. A specific effect on complex I seemed to be involved in drug-induced mitochondria dysfunction. Liver mitochondria from the modified diet group were more susceptible to nimesulide effects on MPT induction. The present work demonstrates that diet manipulation aimed at modifying mitochondrial membrane properties alters the toxicity of mitochondria active agents. This work highlights that diet may potentiate mitochondrial pharmacologic effects or increase drug-induced liabilities.     

IMMUNOSTIMULATING EFFECTS OF ACIDIC POLYSACCHARIDES EXTRACT OF PANAX GINSENG ON MACROPHAGE FUNCTION

ABSTRACT

The root of Panax ginseng C. A. Meyer is one of the most popular natural tonics in oriental countries. In this study, we have isolated polysaccharide fraction of Panax ginseng (ginsan) and examined its effect on the function of murine peritoneal macrophages. When macrophages were treated with ginsan, cytotoxic activity against B16 melanoma cells was significantly induced. In addition, the levels of cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and lnterferon-γ (IFN-γ) were increased and the production of reactive oxygen/nitrogen components such as nitric oxide (NO) and hydrogen peroxide (H₂O₂) was enhanced. Moreover, phagocytic activity was induced in ginsan-treated macrophages compared to the control. The expression of CD14 and l-A^b on murine peritoneal macrophages was increased by the treatment with ginsan, while the expression of CD11b was decreased. Taken together, these results suggest that ginsan has an immunopotentiating effects on macrophages and these abilities could be used clinically for the treatment of diseases such as cancer.     

中西医结合治疗类风湿关节炎的临床效果分析

目的：探讨分析中西医结合治疗类风湿关节炎的临床效果。方法：80例类风湿关节炎患者随机分为两组,其中观察组40例给予甲氨蝶呤＋尼美舒利片＋中药为中西医结合治疗,对照组40例给予甲氨蝶呤＋尼美舒利片为西药治疗,对两组的临床疗效进行对比分析。结果：观察组总有效率为97.5%,对照组总有效率为72.5%,观察组明显高于对照组,差异有统计学意义（P〈0.05）。结论：中西医结合治疗类风湿关节炎的疗效显著,明显优于单纯西药治疗,能够缩短疗程,且无明显的毒副作用。     

儿童口服尼美舒利安全性的系统评价

目的评价儿童口服尼美舒利的安全性。方法计算机检索PubMed、EMBASE、Cochrane图书馆（2011年第3期）、Cochrance临床对照试验数据库、中国生物医学文献光盘数据库、中国期刊全文数据库、中国维普科技期刊数据库和万方数据库,检索时间均从建库至2011年3月。手工检索中国《药品不良反应信息通报》、WHO Pharmaceuticals Newsletter、MHRA Drug Safety Update和FDA Drug Safety Newsletter。获得儿童尼美舒利安全性评价的队列研究、病例对照研究、RCT研究、非随机分组的对照研究和病例报告,此外还获取上市后药物不良反应监测,各国药物监督和管理机构对尼美舒利的风险利益评估、适应证修改等资料。按纳入和排除标准筛选文献,评价文献质量,提取资料。RCT文献采用RevMan 5.0软件进行Meta分析,余文献采用描述性分析,采用WHO-UMC评价体系评价病例报告中不良反应与尼美舒利的关联性。结果未检出儿童尼美舒利安全性评价的队列研究和病例对照研究。检出符合纳入标准的RCT文献43篇,病例报告9篇,尼美舒利上市后不良反应监测1篇。①RCT文献结果：儿童口服尼美舒利不良反应包括胃肠道反应、体温过低、皮疹,肝酶升高和神经系统不良反应（嗜睡或烦躁）。胃肠道反应发生率低于布洛芬（P〈0.000 01）和对乙酰氨基酚（P=0.000 9）;体温过低（P=0.01）和神经系统不良反应（P=0.03）发生率高于布洛芬;ALT和（或）AST升高发生率与布洛芬、对乙酰氨基酚差异均无统计学意义。②病例报告分析结果：报道3例严重肝脏不良反应,其中2例死亡;1例很可能由尼美舒利引起,2例可能由尼美舒利引起;报道5例血尿,均很可能由尼美舒利引起。③上市后不良反应监测结果：未检索到中国尼美舒利不良反应监测数据;印度监测4 092例患儿,报告肾脏不良反应13例,未报告肝脏不良反应。④中国食品药品监督管理局于2008年6月修改尼美舒利说明书,仅用于1岁以上儿童,用于退热疗程不超过3 d;欧洲药品管理局于2007年评估尼美舒利风险和效益后,限制其适应证仅为止痛,不用于退热,且疗程不超过15 d,12岁以下儿童禁用;2011年2月印度卫生部禁止12岁以下儿童使用尼美舒利。结论儿童口服尼美舒利胃肠道反应发生率可能低于布洛芬和对乙酰氨基酚,体温过低和神经系统不良反应发生率可能高于布洛芬,肝酶升高发生率可能与布洛芬和对乙酰氨基酚相似,严重肝脏不良反应有待进一步研究明确其与尼美舒利的因果关系。     

非甾体抗炎药致肝功能损害病例分析

目的:对非甾体抗炎药致肝功能损害病例进行分析,为临床合理用药提供参考。方法:对1例成年女性Still病患者因使用非甾体抗炎药加重肝功能损害进行因果关系分析。结果:患者住院期间口服尼美舒利分散片和维C银翘片可能导致丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)异常升高,经停药并予以还原型谷胱甘肽、多烯磷脂酰胆碱和异甘草酸镁治疗后,ALT和AST逐渐降低。结论:尼美舒利和维C银翘片应慎用于肝功能损害者,同时应定期监测患者肝功能。     

尼美舒利缓释片处方优化研究

目的:优化尼美舒利缓释片的处方。方法:采用正交试验设计,以体外累积释放度为指标,以载药材料羟丙基甲基纤维素(HPMC)、乳糖、聚乙烯吡咯烷酮(PVP)K30无水乙醇溶液的处方用量作为影响因素,设计正交试验筛选缓释片的最佳处方,并进行处方验证试验。结果:优化处方为:HPMC100mg、乳糖50mg、5%PVPK30无水乙醇溶液3mL;以此处方制备的3批缓释片在12h累积释放度约为97%,未出现时滞、突释等现象,体外释药动力学符合零级方程。结论:尼美舒利缓释片处方合理,具有良好的缓释效果。