Efficacy and tolerability of a topical NSAID patch (local action transcutaneous flurbiprofen) and oral diclofenac in the treatment of soft-tissue rheumatism

Summary The efficacy and safety of local action transcutaneous flurbiprofen 40 mg [flurbiprofen LAT] patches and diclofenac sodium tablets, 50 mg b.d., were compared in an open, multicentre, randomized, parallel-group study in patients with soft-tissue rheumatism. Patches were replaced at 12-hourly intervals. Clinical assessments were performed after 7 and 14 days of treatment. Fifty-six patients were treated with flurbiprofen LAT and 53 with diclofenac. Six withdrawals (three from each group) occurred during the treatment period.A statistically significant difference was observed in favour of flurbiprofen LAT for the principal measure, namely the investigator's opinion of overall change in clinical condition: 49/53 (92%) patients treated with flurbiprofen LAT had improved by day 14 compared with 36/49 (73%) patients receiving diclofenac sodium (p=0.03; eligible dataset). There were also statistically significant differences in favour of flurbiprofen LAT for the investigator's assessments of the overall severity of the clinical condition (p=0.03; eligible dataset), for the severity of pain at the region treated (p=0.04; intent-to-treat), and for the severity of tenderness (p<0.001; intent-to-treat). Supplementary analgesia (paracetamol) was required by two patients in the flurbiprofen LAT group and by eight diclofenac-treated patients. The difference in favour of flurbiprofen LAT group and by eight diclofenac-treated patients. The difference in favour of flurbiprofen LAT in the average daily consumption of paracetamol was significant (p=0.04). The patients' assessment of severity of pain on movement also favoured flurbiprofen LAT (p =0.049; eligible dataset), but there were no statistically significant differences in day or night pain or quality of sleep. For the patients' opinion of treatment there was, however, a statistically significant difference in favour of flurbiprofen LAT (p=0.02). Of the patients receiving flurbiprofen LAT, 94% regarded it as a convenient form of treatment.With respect to tolerability 8/56 (14%) patients applying flurbiprofen patches reported a total of nine adverse effects (AEs) (mainly local, mild skin irritations), vs 9/52 (17%) patients receiving diclofenac, who reported 12 AEs. Most AEs in the enteric-coated diclofenac group were of a gastrointestinal nature (one of which was severe). In terms of the proportion of patients reporting AEs related to the digestive system, there was a statistically significant difference in favour of flurbiprofen LAT (p=0.011).In conclusion, local treatment of soft-tissue rheumatism with flurbiprofen LAT was demonstrably superior to benchmark oral therapy with diclofenac sodium over a 2-week period in terms of both efficacy and gastrointestinal tolerability. Flurbiprofen LAT provided both an effective and convenient form of topical SAID treatment.     

氟比洛芬酯对大鼠局灶性脑缺血-再灌注损伤的保护作用

目的 探讨氟比洛芬酯(FA)对脑缺血-再灌注(I-R)损伤的保护作用.方法 40只雄性SD大鼠,随机均分为五组,即A组(I-R)、B组(I-R FA5 mg/kg)、C组(I-R FA 10 mg/kg)、D组(I-R FA 20 mg/kg)和E组(脂微球对照组).采用颈内动脉丝线栓塞致大脑中动脉栓塞(MCAO)模型,再灌注后24、48、72 h观察神经功能缺损评分(NDS评分)并于72 h后处死动物,取大脑切片行10 g/L 2,3,5-氯化三苯四唑(TTC)染色,测量并计算脑梗死容积百分比.结果 72 hNDS评分:B、C、D组明显高于A、E组(P<0.05);梗死容积百分比,B、C、D组明显低于A、E组(P<0.01),B、C、D组间24、48、72 h NDS评分差异无统计学意义;梗死容积百分比B组明显高于C、D组(P<0.05).结论 FA可明显减轻大鼠局灶性脑缺血-再灌注损伤.     

Flurbiprofen-induced stimulation of periosteal bone formation and inhibition of bone resorption in older rats

The skeletal effects of flurbiprofen (Fb), a nonsteroidal antiinflammatory drug, was studied by histomorphometry in 9-month-old retired female breeder, Sprague-Dawley rats. Flurbiprofen was given subcutaneously at 0, 0.2, 0.1, 0.5, 2.5, or 5 mg/kg/d for 21 days. Flurbiprofen had no effect on longitudinal growth, but stimulated radial growth (+200%) over controls. In the tibial shaft, Fb stimulated the mineral apposition rate (+25%), mineral bone formation rate (+100%), and periosteal labeling length (+64%) at the 2.5 and 5.0 mg Fb/kg dose levels, and had no effect on marrow cavity size compared to controls. However, these changes were insufficient to increase cortical bone mass. In the proximal tibial metaphysis, Fb suppressed osteoclasts/mm² of metaphyseal tissue (-47%), osteoclasts/mm of bone surface (-46%), and the osteoclast/osteoblast ratio (-50%), increased the calcified cartilage core population (+100%), and had no effect on osteoblast numbers at all dose levels. There was an insignificant increase in metaphyseal cancellous bone mass. The current study leads to the conclusion that flurbiprofen-stimulated periosteal bone growth was due to direct stimulation of osteoblast recruitment and activity independent of longitudinal bone growth. Further, it confirms early findings in young rats that flurbiprofen induced depressed bone resorption without lowering bone formation. However, because of insufficient treatment time, the older rat did not accumulate bone as the young rats did.     

氟比洛芬酯脂微球注射液对38例癌症疼痛镇痛效果的临床观察

目的：观察氟比洛芬酯脂微球载体注射液（商品名凯纷）治疗癌痛的疗效和副作用。方法：38例未使用阿片类药物的中重度癌性疼痛患者每天静脉注射50mg/5ml氟比洛芬酯脂微球载体注射液．分别就其疗效、生活质量改善情况以及不良反应等方面进行评价。结果：氟比洛芬酯脂微球载体注射液治疗中重度癌痛的有效率为71．05％．生活质量改善情况治疗前后有显著差异（P〈0．05）。但未见一般非甾体类药物常见腹痛、消化道出血等副作用；也未见便秘、恶心、呕吐、嗜睡等阿片类药物常见不良反应。结论：氟比洛芬酯脂微球载体注射液治疗中重度癌痛疗效可靠．生活质量可得到改善．但氟比洛芬酯脂微球载体注射液不良反应发生率较低，可部分作为临床候选药品或口服吗啡替代药。     

氟比洛芬酯对严重烧伤患者急性期应激反应的影响

目的:探讨静脉注射氟比洛芬酯对严重烧伤患者急性期应激反应的影响。方法:收治62例严重烧伤患者,于伤后24 h内入院,随机分为治疗组(氟比洛芬酯镇痛)和对照组(肌内注射镇痛药)。检测镇痛开始前及开始后3 h、18 h、24 h、48 h的血浆胰岛素(INS)、血糖(GLU)、促肾上腺素(ACTH)、去甲肾上腺素(NA)、肾上腺素(AD)和皮质醇(COR)的水平。结果:用药后两组对比,治疗组VAS镇痛效果优于对照组;治疗组镇痛后3~48 h血糖和8~48 h血浆应激激素与镇痛前比较均有所降低,尤其是24~48 h效果明显;组间比较,其血糖和血浆胰岛素水平统计学比较差异有统计学意义(P<0.05或P<0.01)。两组患者均无恶心、呕吐、幻觉以及呼吸抑制、镇静过度等不良反应。结论:氟比洛芬酯能抑制严重烧伤患者急性期应激反应,镇痛效果良好,不良反应少,值得临床推广。     

右美托咪定复合氟比洛芬酯在老年高血压全麻中的应用

目的:观察小剂量右美托咪定复合氟比洛芬酯预防老年高血压全麻患者拔管应激反应的效果和安全性。方法:将血压控制稳定、择期行上腹部手术的90例老年患者随机分成生理盐水对照组(A组)、右美托咪定组(B组)、氟比洛芬酯复合右美托咪定组(C组),均于术毕前30 min微泵静脉注射药物,观察MAP、HR变化,测定血浆肾上腺素(E)、去甲肾上腺素(NE)浓度,记录手术相关指标和不良反应发生情况。结果:3组MAP、HR数值和血浆E、NE浓度均比麻醉前明显增高(P<0.01或P<0.05),B组、C组较A组明显平稳(P<0.01或P<0.05),血浆E、NE浓度的变化更小(P<0.01或P<0.05);B组的唤醒时间、拔管时间明显长于A组和C组(P<0.05);C组不良反应发生率明显低于A组与B组(P<0.05)。结论:小剂量右美托咪定复合氟比洛芬酯,能有效预防老年高血压全麻患者气管拔管引起的应激反应及术后躁动的发生率,不延迟唤醒时间和拔管时间,不良反应少。     

地佐辛联合氟比洛芬酯静脉自控镇痛对开胸术后烦躁状态的影响分析

摘 要 目的： 探讨在开胸手术中采用地佐辛联合氟比洛芬酯麻醉处理的临床效果,以及对患者术后烦躁状态的影响。方法: 98例行开胸手术的患者随机分为对照组与观察组各49例,对照组在手术结束后采用芬太尼与地佐辛静脉自控镇痛,观察组联合应用地佐辛与氟比洛芬酯静脉自控镇痛。观察两组患者临床麻醉效果、药品不良反应及术后躁动状况,比较两组患者不同时点的VAS评分与Ramsay镇静评分。结果:观察组患者在术后2 h与4 h的VAS评分均显著低于对照组（P<0.05）,拔管时与拔管后5 min的Ramsay镇静评分明显好于对照组（P<0.05）;术后苏醒期躁动率和不良反应发生率明显低于对照组（P<0.01）。结论: 开胸手术患者术后联合应用地佐辛与氟比洛芬酯静脉自控镇痛可充分保证镇痛效果,缓解术后躁动情况,具有良好的临床应用价值。     

氟比洛芬酯对表达心脏SCN5A基因HEK293细胞钠电流的影响

目的:利用人胚肾293(HEK293)细胞表达心脏钠通道SCN5A基因并观察氟比洛芬酯(flurbiprofen axetil,FA)对钠通道的影响。方法:野生型SCN5A基因和SCN1B基因共表达于HEK293细胞,应用全细胞膜片钳记录使用FA(0.15μM)前后的钠电流。结果:转染效率约为70%,和使用FA前相比,用药后在每一指令电压上钠电流都减小;在测试电压为-40mV的条件下,钠电流峰值电流密度从(-159.74±63.80)pA/pF降至(-94.48±62.63)pA/pF(n=7,P=0.012);通道稳态激活半激活电压(V1/2)分别为(-51.66±7.69)mV和(-58.19±2.45)mV(n=7,P=0.048);稳态失活半激活电压(V1/2)分别为(-83.55±3.21)mV和(-85.25±4.78)mV(n=7,P=0.041);通道失活后恢复τ分别为(33.86±23.18)ms和(67.71±58.58)ms(n=7,P=0.048)。结论:FA可以减小各测试电压下的钠电流峰值(电压电流曲线向上漂移);加速通道的电压依赖性激活,促进通道的电压依赖性失活,失活后恢复变慢。     

不同方式氟比洛芬酯复合芬太尼术后镇痛效果的比较:前瞻性、多中心、随机、双盲、对照、平行分组研究

目的 比较不同方式氟比洛芬酯复合芬太尼用于术后镇痛的效果.方法 本研究为前瞻性、多中心、随机、双盲、对照、平行分组研究.选择2010年1月至2010年10月择期行骨科、胸外科、肝胆外科等大中型手术的病人,ASA分级Ⅰ或Ⅱ级,年龄14 ～ 91岁,体重35 ～ 95 kg,采用随机数字表法,将其分为3组,A组:术毕即刻静脉注射氟比洛芬酯100 mg,然后芬太尼1.0 mg用生理盐水稀释至100 ml,进行PCIA;B组:氟比洛芬酯200 mg+芬太尼0.6 mg用生理盐水配稀释至100 ml,进行PCIA;C组:术毕即刻静脉注射氟比洛芬酯100 mg,氟比洛芬酯200 mg+芬太尼0.6 mg用生理盐水稀释至100 ml进行PCIA.3组背景输注速率2 ml/h,PCA量2 ml,锁定时间10 min.分别于术毕、术后4、8和24 h时记录静态和动态VAS评分和镇静评分.术后24 h内记录镇痛有效、过度镇静、恶心、呕吐、瘙痒、头晕、嗜睡和呼吸抑制的发生情况.术后24和48 h时随机选择一个中心B组镇痛泵内容物,取样后进行微生物培养试验.结果 共完成2596例,其中A组875例、B组946例、C组775例.与A组比较,B组术毕、术后4、8和24h时静态和动态VAS评分和各时点镇静评分均降低,C组术毕、术后4、8h时静态和动态VAS评分均降低,术后4、8h时镇静评分升高,2组镇痛有效率均升高,B组过度镇静发生率降低,C组过度镇静发生率升高,2组术后恶心和呕吐的发生率降低,C组术后头晕发生率降低(P＜0.05);与B组比较,C组各时点静态和动态VAS评分、镇痛有效率、恶心、呕吐以及瘙痒发生率差异无统计学意义(P＞0.05),术毕、术后4、8h时镇静评分升高,过度镇静发生率升高,头晕发生率降低(P＜0.05).术后24、48 h时泵内容物标本细菌和真菌培养均为阴性.结论 对于大中型手术病人,氟比洛芬200 mg复合芬太尼0.6 mg PCIA(背景输注速率2 ml/h,PCA量2 ml,锁定时间10 min)术后镇痛的效果更佳,且不良反应发生几率低.     

氟比洛芬酯对骨癌大鼠肾功能、凝血功能及其血小板聚集的影响

目的 连续7d腹腔注射氟比洛芬酯注射液,研究其对骨癌痛大鼠肾脏、凝血功能、血小板聚集影响. 方法 36只成熟雌性SD大鼠完全随机分为6组:肿瘤+生理盐水组(C组)、肿瘤+氟比洛芬酯10 mg· kg1·d-1组(CK10组)、肿瘤+氟比洛芬酯25 mg·kg-1·d-1组(CK25组)、肿瘤+氟比洛芬酯50 mg· kg-1·d-1组(CK50组)、氟比洛芬酯50 mg· kg-1·d-1单纯组(K50组)和假手术组+生理盐水组(sham组),每组6只.制作骨癌痛模型14 d后,每天分别腹腔注射相应剂量氟比洛芬酯或生理盐水2次,连续7d后处死大鼠.腹主动脉采血,检测血尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)、Na+、K+、凝血酶原时间(protrombin time,PT)、活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、纤维蛋白原(fibrinogen,Fib)、血小板聚集功能(platelet aggregation,PA)及其观察肾病理学变化.结果 腹腔给予氟比洛芬酯7d后,分别与sham组和C组比较,CK50组(9.9±1.5) mmol/L、K50组(9.7±1.4)mmol/L血BUN水平明显增高(P＜0.05),CK50组(137±8) mmol/L、K50组(138±8)mmol/L Na+和CK50组(3.9±0.3)mmol/L、K50组(3.9±0.4) mmol/L K+显著降低(P＜0.05),Cr、PT、APTT、Fib和PA值变化无统计学意义(P＞0.05);CK10、CK25组血BUN、Cr、PT、APTT、Fib、Na+、K+和PA值分别与sham组、C组比较,差异无统计学意义(P＞0.05).CK50、K50组病理学变化为肾小球缩小,肾小球毛细血管充盈不足;C组、sham组、CK10、CK25组肾组织结构清晰,未见异常变化. 结论 腹腔重复注射不同剂量氟比洛芬酯对骨肿瘤大鼠凝血功能及其血小板聚集功能无明显影响,然而大剂量氟比洛芬酯(50 mg·kg-1·d-1)影响尿素氮、钠钾离子的代谢及肾小球毛细血管充盈.