RP-HPLC测定血浆中双氯芬酸钠的研究

本文利用反相高效液相色谱法(RP-HPLC)对双氯芬酸钠(DS)血浓度的测定进行了研究,建立了灵敏、精确、简便、重现性好的分析方法。适用于药代动力学的研究。条件是在0.2mol/L NaAc-HAc缓冲溶液(pH5.0)中以乙醚-二氯甲烷3:1(V/V)提取。固定相为YWG C_(18)H_(37),流动相为MeOH-0.02mol/L HAc(pH 5.5)65:35(V/V)、卡马西平(CZ)作内标,UV 280nm检测。线性范围0.24～22.8μg/ml,γ=0.999 9。最低检测浓度为60ng/ml。提取回收率为95.83％～97.58％。方法回收率为100.33％～106.46％。天内及天间精密度(GV)各为0.55％～1.11％及1.40％～2.91％。     

Attenuated gastropathy but not enteropathy of diclofenac–cholestyramine complex in rats

Diclofenac is a nonsteroidal anti‐inflammatory drug (NSAID) widely prescribed for pain and inflammation. Theoretically, the gastrointestinal (GI) complications of diclofenac could be minimized by administering a diclofenac resinate formulation, such as Flotac, where GI mucosal contact with free NSAID is minimized by its complexing with the cholestyramine resin. The objective of the present study was to investigate the influence of cholestyramine co‐treatment on diclofenac enteropathy in fed rats and diclofenac gastropathy in fasted rats. Male Sprague‐Dawley rats were gavaged with diclofenac (50 mg/kg), diclofenac (50 mg/kg) plus cholestyramine (50 mg/kg), or an equivalent amount of Flotac, a 1:1 wt/wt mixture of diclofenac and cholestyramine presently used in human therapeutics in Mexico. Ulceration of the GI tract, serum proteins, and bile salts were assessed at 3, 12, or 24 h. Cholestyramine alone produced no detectable alterations in small intestinal integrity or serum bile salts levels. Fed rats given Flotac or diclofenac plus cholestyramine showed patterns of small intestinal ulceration and serum protein decline that were similar to rats given only diclofenac. Thus, no influence on enteropathy was detected. In contrast, fasted rats given Flotac showed a modest reduction in the number and length of gastric lesions compared to rats given diclofenac. The observed attenuation of gastric lesions with Flotac is consistent with a role for direct cytotoxicity in NSAID gastropathy. Drug Dev. Res. 64:19–27, 2005. © 2005 Wiley‐Liss, Inc.     

Day case laparoscopy: a survey of postoperative pain and an assessment of the value of diclofenac

A randomised, controlled study was undertaken to assess the postoperative pain and side effects experienced by patients undergoing day case diagnostic laparoscopy and laparoscopic sterilisation, and to evaluate the effectiveness in these patients of peroperative diclofenac. Patients undergoing laparoscopic sterilisation had significantly higher pain scores at one hour postoperatively, and at discharge, than patients undergoing diagnostic laparoscopy (p less than 0.01) but there were no significant differences in pain scores 24 hours after discharge. The incidence of postoperative side effects following discharge from hospital was high, but there were no significant differences between the groups. Diclofenac had no significant effect in either group on the severity of postoperative pain, or the incidence of postoperative side effects.     

Two Non-steroidal Anti-inflammatory Drugs,Niflumic Acid and Diclofenac,Inhibit the Human Glutamate Transporter EAAT1 Through Different Mechanisms

We investigated the effects of non-steroidal anti-inflammatory drugs on substrate-induced currents of l-glutamate (l-Glu) transporter EAAT1 expressed in Xenopus laevis oocytes. Niflumic acid (NFA) and diclofenac inhibited l-Glu-induced current through EAAT1 in a noncompetitive manner. NFA produced a leftward shift in reversal potential (E_rev) of l-Glu-induced current and increased current amplitude at the potentials more negative than ?100 mV. Diclofenac had no effects on E _rev and inhibited the current amplitude to the same extent at all negative potentials. These results indicate that NFA and diclofenac inhibit the l-Glu-induced EAAT1 current via different mechanisms.[Supplementary methods and Figure: available only at http://dx.doi.org/10.1254/jphs.09260SC]     

Oral celecoxib versus oral diclofenac for post-perineal repair analgesia after spontaneous vaginal birth: a randomised trial

OBJECTIVE: To compare oral celecoxib with oral diclofenac as pain reliever after perineal repair following normal vaginal birth. METHODS: One hundred and sixty-four and 165 women, respectively, were randomised to 200 mg celecoxib or to 100 mg diclofenac orally 12 hourly for 24 h after perineal repair. A ten-point visual analog scale (VAS) for pain recorded at one, two, four, eight, 12 and 24 hours at rest and when mobilising was the primary outcome. RESULTS: Repeated measures analysis of variance showed a larger reduction of VAS pain score at rest with celecoxib compared to diclofenac (P = 0.044). Mean VAS pain score at rest was 2.2 versus 2.7, 2.1 versus 2.5, 1.8 versus 2.2, 1.6 versus 1.6, 1.3 versus 1.4 at one, two, four, eight, 12 and 24 hours, respectively, for celecoxib versus diclofenac. The difference in pain score when mobilising was not significant (P = 0.75). Univariate analyses with the Student's t-test indicated significantly lower pain score at rest only at one, two and four hours with celecoxib. Randomisation to celecoxib was associated with less upper gastrointestinal symptoms reported: 38 of 163 (23.3%) versus 57 of 165 (34.5%) (relative risk 0.67 95% CI 0.48-0.96: P = 0.029) but additional analgesia for breakthrough pain was not significantly different eight of 161 (5.0%) versus 18 of 165 (10.9%) (relative risk 0.46 95% CI 0.20-1.01: P = 0.065). CONCLUSION: Celecoxib was associated with a slightly lower VAS pain score at rest and less upper gastrointestinal symptoms were reported when compared to diclofenac.     

双氯酚酸钾颗粒与双氯酚酸钾片的人体生物等效性研究

目的 :进行双氯酚酸钾颗粒与双氯酚酸钾片单剂双交叉生物等效性研究。方法 :男性健康志愿者18名自身交叉单剂量口服双氯酚酸钾颗粒与双氯酚酸钾片50mg ,采用高效液相色谱法测定双氯酚酸钾经 -时血药浓度 ,计算其药代动力学参数与相对生物利用度。结果 :双氯酚酸钾颗粒与双氯酚酸钾片主要药代动力学参数T1/2( β) 分别为 (3 022±0 698)h和 (2 980±0 744)h ,Tpeak 分别为 (0 972±0 188)h和 (1 000±0 000)h ,Cmax 分别为 (1 57±0 211) μg/ml和 (1 664±0 243) μg/ml,AUC0～12 分别为 (4 115±0 422) μg/(ml·h)和 (4 217±0 293) μg/(ml·h) ,AUC0～∞分别为 (4 59±0 330) μg/(ml·h)和 (4 639±0 383) μg/(ml·h)。两药各药代动力学参数间均无统计学差异 ,双氯酚酸钾颗粒相对生物利用度 (F)为 (99 47±9 79) %。结论 :双氯酚酸钾颗粒与双氯酚酸钾片具有生物等效性     

双氯芬酸钠丝素蛋白 - 壳聚糖缓释微球的制备及体内外评价

 目的 以双氯芬酸钠（ diclofenac sodium ， DS ）为模型药物，丝素蛋白（ silk fibroin ， SF ） / 壳聚糖 (chitosan ， CS)(1 ∶ 1) 为复合载体制备双氯芬酸钠丝素蛋白 / 壳聚糖缓释微球 (DS-SF/CS-MS) ，并考察其体内外相关性。 方法 采用乳化 - 化学交联固化法制备 DS-SF/CS-MS ；动态透析法考察了微球的体外释放特性；以 DS 溶液对照，大鼠分别 ig 相同剂量的 DS-CS-MS 和 DS-SF/CS-MS 后， HPLC 测定血浆中 DS 浓度， 3P97 程序计算药动学参数。 结果 DS-SF/CS-MS 的载药量和包封率分别为 (9.88±0.49)% 和 (50.35±0.92)% ，平均粒径为 (26.54±1.39) μm ； DS-SF/CS-MS 在不同 pH 的释放介质中均遵循 Higuchi 方程，其缓释效果明显优于双氯芬酸钠 - 壳聚糖微球 (DS-CS-MS) ；大鼠体内的双氯芬酸钠血药浓度经时曲线均符合一室模型， 3 种制剂的 MRT 分别为 (4.11±0.03) ， (6.92±0.39) 和 (24.35±0.27)h 。 DS-SF/CS-MS 的 MRT 与 <> t _1/2 明显延长，其相对生物利用度为溶液剂的 140.0% 。 结论 SF/CS-MS 的性能优异，有望成为一种低毒性的新型缓控释载体材料。     

高效液相色谱法测定炎痛净乳膏中双氯芬酸钠和苯佐卡因的含量

目的：测定炎痛净乳膏中双氯芬酸钠和苯佐卡因的含量。方法：高效液想象以谱法，甲醇为提取溶剂，地西泮为内标，No-va-PakC18色谱柱，甲醇-水-冰醋酸（80：20：0.5)为流动相，检测波长为283nm。结果：双氯芬酸钠和苯佐卡因在5μg/ml-40μg/ml范围内，其浓度与峰面积均呈良好的线性关系（r=0.9999)，平均回收率分别为101.0%,RSD=1.21%,99.8%,RSD=0.62%。结论：本法专属性强，操作简便，结果准确。     

电针与双氯灭痛治疗腰椎间盘突出症的疗效观察

背景研究表明针刺对治疗坐骨神经痛有较高的有效率,非类固醇类药物,如双氯灭痛也被广泛用于治疗坐骨神经痛,但针刺和双氯灭痛分别治疗坐骨神经痛的疗效对比如何亟待研究.目的比较电针刺与双氯灭痛治疗腰椎间盘突出症引起的坐骨神经痛的疗效.设计随机对照研究.地点和对象本研究在巴基斯坦伊斯兰堡中国针灸中心完成,对象为2001-02/2002-10该中心门诊治疗的腰椎间盘突出症患者40例.方法随机分为电针组23例,电针刺25 min/d,治疗7 d.药物组17例,口服双氯灭痛片50 mg/次,3次/d,治疗7 d.主要观察指标两组治疗前后直腿抬高实验(SLR),臀部、大腿后侧及小腿压痛、麻木感.结果治疗后电针组直腿抬高角度明显大于药物组(t=2.179,P＜0.05);电针组臀部压痛减轻的VSA分数明显小于药物组(t=2.224,P＜0.05).但压痛的减轻在大腿后和小腿部在两组间没有区别(大腿t=1.912,小腿t=1.580,P＞0.05).在电针组SLR增加20°以上的患者数多于药物组(x2=4.817,P＜0.05).同样,电针组臀部压痛减轻在20分以上的患者数多于药物组(x2=5.028,P＜0.05).但大腿后和小腿部压痛的减轻在20分以上的患者数两组间没有明显区别(大腿x2=0.583;小腿x2=1.081,P＞0.05).足部麻木感的减轻两组间没有明显区别(x2=0.680,P＞0.05).结论对于提高SLR角度和减轻针刺区的压痛电针刺效果优于双氯灭痛治疗.在远离穴位的区域两者对减轻压痛的作用无明显区别.