双氯灭痛在正常人体内的药物动力学研究

采用反相高效液相色谱法测定了１０例健康人单剂量口服７５ｍｇ双氯灭痛片剂后血浆药浓度，研究了该药物在中国人体内药物动力学。经用ＰＫＢＰ－Ｎ＿１程序包在计算机上拟合计算表明，双氯灭痛口服给药多数人表现为二房室模型。其主要药动学参数分别为：Ｔ＿（α１／２）＝０．４０±０．１１ｈ，Ｔ＿（β１／２）＝１．７７±０．５ｈ，Ｔ＿（ｍａｘ）＝１．７８±０．３２ｈ，Ｃ＿（ｍａｘ）＝１．８７±０．９μｇ／ｍｌ，ＡＵＣ＝３．８１±１．７μｇ／（ｍｌ·ｈ）。结果表明，中国人体内的药动学参数与所报道的外国人体内相似。     

双氯芬酸凝胶的稳定性研究

本文采用高效液相色谱法测定双氯芬酸凝胶中双氯芬酸的含量，以经典恒温法预测其稳定性，结果表明该制剂降解呈一级反应，室温（２５℃）有效期为２．６年。     

双氯芬酸胆碱滴眼液对兔眼炎症模型抗炎效果观察

目的；观察双氯芬酸胆碱滴眼液的抗炎效果。方法：新西兰大白兔36只，随机分为3组，分别用辣椒酊、斑蝥酊和电烫伤刺激兔眼致炎症模型，1.0g/L双氯芬酸胆碱滴眼滴眼，以醋酸可的松滴眼液和生理盐水为对照，观察其对角膜、虹膜、结膜炎的治疗效果。结果：1.0g/L双氯芬酸胆碱滴眼液可显著减轻刺激引起的兔眼前节炎症反应的强度，消除炎症反应积分与醋酸可的松滴眼液相似。结论：双氯芬酸胆碱滴眼液可作为一种新的非甾体抗炎滴眼药进行开发应用。     

双氯芬酸钠栓用于老年全膝关节置换术围术期镇痛的临床研究

目的探讨双氯芬酸钠栓对老年全膝关节置换术(TKA)围术期镇痛疗效。方法将92例TKA手术患者分成2组,对照组予美洛昔康分散片口服7.5 mg/次,2次/d,术后静脉镇痛泵镇痛,研究组在对照组基础上加用双氯芬酸钠栓50 mg纳肛,观察不同镇痛模式在术后24、48 h、术后3 d、1周、2周疼痛视觉模拟评分(VAS)、膝关节活动度和不良反应变化情况。结果 2组术后VAS评分均不断下降,关节活动度均不断升高,研究组术后24、48 h、术后3 d、1周、2周在静息和活动VAS评分上均显著低于对照组(P0.05),而在主动和被动关节活动度上均显著高于对照组(P0.05);2组恶心呕吐、尿潴留、呼吸抑制、头晕头痛等不良反应发生率比较无显著差异(P0.05)。结论双氯芬酸钠栓辅助治疗能提高TKA围术期镇痛效果,提高关节活动度,且不良反应低。     

Gastrointestinal tolerability of metamizol,acetaminophen, and diclofenac in subchronic treatment in rats

The gastrointestinal tolerability of metamizol and acetaminophen [weak cyclooxygenase (COX) inhibitors] in comparison with diclofenac (nonselective cyclooxygenase inhibitor) was evaluated in subchronic treatments in rats. Wistar rats recived 60 mg/kg body weight of metamizol and acetaminophen, and 3 mg/kg body weight of diclofenac by oral route twice daily for 14 days. Myeloperoxidase activity, an index of neutrophil infiltration, COX expression and the effects on blood parameters used as indicators of liver and renal functions were also studied. Metamizol and acetaminophen did not cause apparent gastrointestinal lesions; in contrast diclofenac showed swelling and an increased thickness on the distal intestinal mucosa. Myeloperoxidase activity was significantly increased in the small bowel with diclofenac treatment. In gastric mucosa the expression of the cyclooxygenase-1 was not affected and the expression of cyclooxygenase-2 was not observed. Diclofenac treatment significantly diminished hematocrit, hemoglobin, and corpuscular volume and increased the number of platelets. Aspartate aminotransferase and -glutamyltransferase activity were also altered and, regarding the renal biochemical parameters, the animals treated with diclofenac had increased urea values. In contrast, acetaminophen treatment did not affect either of these parameters and metamizol increased only the alanine aminotransferase activity. Under our experimental conditions, metamizol and acetaminophen seem to be safe drugs. In contrast, with diclofenac treatment blood loss and anemia are observed which could stem from the small intestinal injury. Moreover, this drug could to impair kidney function.     

The effect of non-steroidal anti-inflammatory drugs on the endothelial function of patients with osteoarthritis in short term

Objective: Our primary aim was to test whether non‐steroid anti‐inflammatory drug (NSAID) use may account for endothelial dysfunction (ED) in the acute period. Additionally, we also aimed to compare the effect of diclofenac and naproxen on endothelial function. Methods: Forty patients with osteoarthritis (OA) were included in the study. Subjects currently receiving NSAIDs were asked to discontinue their anti‐inflammatory medications (for at least 5 days) before the study. After the wash‐out period, all subjects underwent vascular ultrasound measurements. Following baseline vascular imaging, patients were randomly assigned in a 1 : 1 ratio to receive either diclofenac (75 mg twice daily, n = 20), or naproxen (500 mg twice daily, n = 20) for 7 days. Endothelial function was evaluated by using the flow‐mediated dilatation (FMD) method, at baseline, and after 1 week of NSAID treatment. Results: There were 40 OA patients (4 male, 36 female). The median age of the patients was 60 ± 14 years. There were equal numbers of subjects in each treatment group. Age, sex distribution, body mass index, serum lipids, erythrocyte sedimentation rate, C‐reactive protein and fasting glucose levels were similar between the diclofenac and naproxen groups (P > 0.05). The brachial artery diameter (BAD), endothelium‐dependent vasodilatation (FMD%) and nitroglycerin‐induced endothelium‐independent vasodilatation (NTG%) values were not different between pretreatment and on the seventh day in the NSAID treatment groups (P > 0.05). Subgroup analysis also showed similar values of BAD, FMD%, and NTG% between naproxen and diclofenac groups (P > 0.05). Conclusion: Our results suggest that nonselective cyclo‐oxygenase antagonists naproxen and diclofenac have no effect on endothelial function during short‐term use.     

Aging Enhances Susceptibility of Diclofenac-Treated Rats to Gastric Ulceration, While Attenuating Enteropathy

Although clinical reports note aging and gender as risk factors for NSAID therapy associated gastroenteropathy, neither variable has been examined in an animal model. We addressed this unknown by comparing the responses of young (4 months) and old (22 months) rats of both genders to oral treatment with diclofenac (10 or 50 mg/kg). Diclofenac produced gastric ulcers only in old rats, with markedly larger lesions in females. In contrast, the small intestines in old rats of both genders given the 50 mg/kg dosage had >30% fewer ulcers and a fourfold decrease in area of ulceration compared to young rats. The small intestine was the only site of lesions after the 10 mg/kg dosage and showed one gender influence, namely, a transiently faster time course of ulcer development in females. Old and young rats given 50 mg/kg showed similar declines in serum levels of the vascular permeability indices-total protein and albumin-despite reduced intestinal damage in the old animals, which suggests additive vascular leakage across the gastric lesions that were evident only in old animals. Serum biochemistry showed no evidence of hepatotoxicity or dysfunction, consonant with small intestine as the primary target for diclofenac toxicity in rats. We provide the first experimental evidence for an aging influence on the gastrointestinal target site of a nonaspirin NSAID.     

Systematic Reviews Published in the January 2013 Issue of the Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD but monthly online (http://www.thecochranelibrary.com). The January 2013 issue (1st DVD for 2013) contains 5328 complete reviews, 2291 protocols for reviews in production, and almost 19,600 short summaries of systematic reviews published in the general medical literature. In addition, there are citations of 681,000 randomized controlled trials, and 15,700 cited papers in the Cochrane methodology register. The health technology assessment database contains some 12,000 citations. One hundred and twenty-two new reviews have been published in the previous 3 months, of which five have potential relevance for practitioners in pain and palliative medicine. The impact factor of the Cochrane Library stands at 5.715. Readers are encouraged to access the full report for any articles of interest as only a brief commentary is provided.