COX-2抑制剂塞来昔布临床用药对胃肠道安全性观察

目的使用COX-2抑制剂塞来昔布和传统NSAIDS双氯芬酸;观察对患者止痛效果和胃肠道安全的影响。方法选择骨关节炎（OA）患者120例,分为两组。一组使用传统NSAIDS双氯芬酸,一组使用COX-2抑制剂塞来昔布胶囊,两组用药分阶段至半年评估对胃肠道耐受性影响。结果NSAIDS组胃肠道不耐受性半年停药80％,塞来昔布组胃肠道不耐受性半年停药只占38％。两组止痛效果相当。结论COX-2抑制剂塞来昔布用于骨关节炎治疗止痛效果满意,胃肠道安全性好。     

塞来昔布对膝骨性关节炎的疗效及副作用观察

目的 观察塞来昔布(Celecoxib)对膝骨性关节炎的疗效及副作用. 方法 塞来昔布组56例, 剂量200 mg*d-1; 双氯芬酸钠组30例, 剂量150 mg*d-1, 分3次口服. 疗程均为6周, 观察膝骨关节炎疼痛缓解程度、关节功能恢复状况、关节积液肿胀消退状况及服药期间出现的副作用. 结果 塞来昔布和双氯芬酸钠对膝骨关节疼痛比较P＞0.05, 差异无显著性. 胃肠道副作用明显比双氯芬酸钠少(χ2=9.740, P＜0.005). 结论 塞来昔布对膝骨关节炎疼痛及关节功能恢复与双氯芬酸钠最大治疗剂量相当,对关节积液的吸收及关节肿胀消退作用明显, 并具有良好的胃肠道耐受性.     

环氧酶抑制剂对大鼠血小板聚集的影响

目的：研究环氧酶抑制剂艾瑞昔布、氯吲昔布、美洛昔康、塞来昔布和吲哚美辛对环氧酶-1（COX-1）和环氧酶-2（COX-2）的选择性及对大鼠血小板聚集的影响，探讨环氧酶选择性抑制与血小板聚集之间的关系。方法：利用A23187刺激的小鼠腹腔巨噬细胞模型检测COX-1表达的变化；利用LPS诱导的小鼠腹腔巨噬细胞模型检测COX-2表达的变化；利用花生四烯酸和胶原作为刺激剂诱导血小板聚集模型检测化合物对大鼠血小板聚集的影响。结果：上述化合物对COX-1和COX-2的表达均有明显的抑制作用，其对COX-1和COX-2抑制率IC50的比值分别为：艾瑞昔布IC50 coxl／IC50 cox2为6．7；氯吲昔布IC50 cox-1／IC50cox-2为3．5；美洛昔康抑制IC50cox-1／IC50COX-2为3．0；塞来昔布C50cox-1／IC50cox-2为61．5；吲哚美辛抑制IC50cox-1／IC50COX-2为0．66。艾瑞昔布、氯吲昔布、美洛昔康和吲哚美辛抑制花生四烯酸诱导的大鼠血小板聚集的IC50分别为2．98×10-6 mol／L、1．13×10-5 mol／L、6．80×10-6mol／L和1．82×10-6mol／L；其抑制胶原诱导的大鼠血小板聚集的Ic50分别为2．89×10-6mol／L、3．24×10-6mol／L、5.4×10-8mol／L和1．87×10-7mol／L。塞来昔布在10-5mol／L，浓度时对花生四烯酸和胶原诱导的血小板聚集无明显抑制作用。结论：上述化合物对环氧酶选者性抑制南强到弱的顺序依次为塞来昔布、艾瑞昔布、氯吲昔布、美洛昔康和吲哚美辛。随环氧酶抑制的选择性降低，化合物对血小板聚集制作用逐渐增强。     

The Effect of Celecoxib on Memory Function and Expression of Caspase-3 Protein following Traumatic Brain Injury in Rats

目的:探讨选择性环氧合酶-2(COX-2)抑制剂塞来昔布对重型颅脑创伤大鼠脑组织中COX-2和半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)蛋白表达及学习记忆功能的影响.方法:将成年Wistar大鼠48只随机分为脑创伤组、塞来昔布治疗组、假手术组和正常对照组,每组12只.建立大鼠重型闭合性颅脑创伤模型,各组均在相应的时间点处死取材,应用免疫组化法和Western blot法检测COX-2及Caspase-3蛋白表达.再取24只大鼠随机分为脑创伤组、塞来昔布治疗组、假手术组及正常对照组,进行水迷宫测试.结果:脑创伤组COX-2及Caspase-3的水平高于正常对照组及假手术组,塞来昔布治疗组的COX-2及Caspase-3水平低于脑创伤组,差异有统计学意义(P＜0.05).脑创伤组大鼠脑创伤后7～10d搜索平台所需的时间均大于其他3组,差异有统计学意义(P＜0.05),其他3组间比较差异无统计学意义(p＞0.05).结论:塞来昔布对大鼠重型颅脑创伤有脑保护作用,其可降低COX-2、Caspase-3的表达,抑制脑损伤后的炎症反应和细胞凋亡,能够改善脑创伤后的学习记忆障碍.     

双氯芬酸钠和塞来昔布治疗类风湿关节炎的临床疗效及用药安全性

目的：研究双氯芬酸钠与塞来昔布治疗类风湿关节炎的临床疗效以及用药安全性。方法择取我院自2014年8月至2015年6月收治的98例类风湿关节炎患者,将患者随机分为两组,分别为实验组和对照组,两组各49例患者,对两组患者行以不同的治疗方法。对照组行以双氯芬酸钠药物治疗,实验组行以塞来昔布药物治疗,并对比两组患者治疗效果、患者实验室指标变化以及患者治疗过程中的不良反应。结果使用塞来昔布药物治疗的实验组的效果较佳,且不良反应较少,对照组的治疗效果相对较差,两组的对比有统计学意义（ P＜0.05）。结论塞来昔布药物对于类风湿关节炎疾病的治疗效果较佳,值得应用。     

塞来昔布治疗膝骨关节炎疗效观察

目的：探讨塞来昔布治疗膝骨性关节炎的临床效果。方法：回顾2006年6月～2010年6月在本院就诊的膝骨性关节炎门诊患者,患者随机分为两组,一组口服塞来昔布（塞来昔布组）,另一组口服双氯芬酸钠双释放肠溶胶囊（双氯芬酸钠组）。两组患者均同时接受膝关节局部理疗。结果：80例患者治疗期间,塞来昔布组胃肠道的不良反应发生率明显降低。从治疗第2周起,患者临床症状开始缓解,Lequesne指数下降,治疗4、6周时Lequesne指数明显下降,塞来昔布组改善更明显,差异有统计学意义（P〈0.05）,经过6周的治疗,塞来昔布组患者的症状得到显著改善,停药2周后,上述指标维持在6周治疗时的相似水平。结论：塞来昔布对消化系统的不良反应明显低于传统非甾体类抗炎药,而保留了非甾体类抗炎药对关节炎的治疗功效。     

不同类型非甾体抗炎药物对脊柱术后椎体间植骨融合影响的相关研究

目的比较不同类型非甾体抗炎药物对椎体间植骨融合的影响差异性,阐明椎体间植骨融合的生物学关键环节和总体机制。方法选择成年雄性日本大耳白兔,建立脊柱融合的动物模型。分为双氯芬酸钠组、塞来昔布组和对照组,在术后即可开始喂食相应药物持续2周后停止。在术后4、8、12周分别取各组动物融合节段行大体标本。评估各实验兔的Nilsson骨愈合组织学评分、Lane-Sandhu骨愈合X线评分,融合节段(L_(3~4))与相邻未融合节段(L_(4~5))的生物力学强度比值,进行组织学、影像学和生物力学的定量比较和统计学分析。结果本研究共纳入45只脊柱融合动物模型,双氯芬酸钠组、塞来昔布组和对照组各15只。术后4周时,双氯芬酸钠组和塞来昔布组的Nilsson骨愈合组织学评分、Lane-Sandhu骨愈合X线评分和生物力学强度比值显著低于对照组(P 0.05)。术后8周和12周时,双氯芬酸钠组的Nilsson骨愈合组织学评分、Lane-Sandhu骨愈合X线评分和生物力学强度比值显著低于对照组(P 0.05),而塞来昔布组与对照组比较无统计学差异。结论选择性COX-2和非选择性COX抑制剂在脊柱术后早期对植骨融合均有负面影响,在术后中后期,选择性COX-2非抑制剂对骨融合的负面影响消失,而非选择性COX抑制剂的负面影响仍存在。     

昔布类药物的临床安全性

昔布类药物即高选择性COX-2抑制剂,通过选择性抑制COX-2,阻断花生四烯酸合成前列腺素而发挥抗炎镇痛作用[1],可减少传统NSAID药物消化系统的不良反应,主要品种有罗非昔布、塞来昔布、伐地昔布、帕瑞昔布、依托昔布及卢米昔布等.其中罗非昔布（万络）在2004年9月由于心血管不良反应撤市,引起人们对昔布类药物安全性的争论,为客观评价昔布类药物的临床安全性,现综述近年来国内外关于该类药物的文献和报道,分别对以上几种昔布类药物总结如下.     

环氧化酶-2抑制剂与抗癌药对Caco-2细胞抑制的相互作用

目的:探讨环氧化酶-2(COX-2)抑制剂与细胞毒抗癌药对人结肠腺癌细胞Caco-2抑制的相互作用.方法:用MTT法测定尼美舒利和塞来昔布与细胞周期非特异性药物CDDP和细胞周期特异性药物5-Fu并用时Caco-2细胞的抑制作用.结果:塞来昔布1mg/L～10mg/L与CDDP 1mg/L合用或塞来昔布1mg/L～5mg/L与5-Fu 0.5mg/L合用,对Caco-2细胞的抑制有相加作用.更高浓度(15mg/L～20mg/L)的塞来昔布与CDDP 1mg/L合用或塞来昔布10mg/L～20mg/L与5-Fu 0.5mg/L合用,引起拮抗作用.尼美舒利1mg/L～20mg/L与CDDP 1mg/L合用,对Caco-2细胞的抑制呈拮抗作用,而与5-Fu 1mr/L合用,对Caco-2细胞的抑制呈相加作用.结论:低浓度的塞来昔布和CDDP合用,呈相加作用,但当塞来昔布的浓度增大时,就转为拮抗.尼美舒利和CDDP合用时,无论浓度高低,都呈拮抗作用.     

选择性COX-2抑制剂的心血管安全性评价

目的：研究以罗非昔布、塞来昔布、伐地昔布、鲁米昔布为代表的选择性COX-2抑制剂在临床应用的安全性。方法：查询国内外相关文献资料并结合临床实践进行回顾性研究。结果：罗非昔布、塞来昔布、伐地昔布、鲁米昔布等都有增加心血管不良事件的危险,同时罗非昔布的心血管风险要高于塞来昔布。结论：心血管危险是COX-2抑制剂的“类效应”,所以在临床应用这类药物时．应当加强合理的监管措施;仍需对COX-2抑制剂在心血管系统的安全性进行深入研究。     

Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults: a randomized, controlled trial

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) nonspecifically inhibit cyclooxygenase-1 (COX-1), an enzyme critical to normal platelet function, and COX-2, which mediates inflammatory response mechanisms. Celecoxib, an antiarthritic agent that inhibits COX-2 but spares COX-1 at therapeutic doses, is expected to have minimal effects on platelet function. A double-blind, randomized, placebo-controlled study of 10 days' duration was conducted in 24 healthy adults to compare the effects on platelet function of a supratherapeutic dose of celecoxib (600 mg bid) with a standard dose of naproxen (500 mg bid), a conventional NSAID. Ex vivo platelet aggregation in response to standard agonists (collagen, arachidonate, or U46619 [a thromboxane A2 receptor agonist]), bleeding time, and serum thromboxane B2 (TxB2) level were measured. Unlike celecoxib or placebo, naproxen produced statistically significant reductions in platelet aggregation and serum TxB2 levels and increased bleeding time. The results indicate that even at supratherapeutic doses, celecoxib will not interfere with normal mechanisms of platelet aggregation and hemostasis, supporting the premise that celecoxib is COX-1 sparing relative to conventional NSAIDs.     

Are rofecoxib and celecoxib safer NSAIDS?

NSAIDs work by inhibiting the enzyme cyclo-oxygenase (COX), responsible for prostaglandin synthesis. This enzyme exists in two isoforms, COX-1 and COX-2. Inhibition of COX-1 is thought to be the main cause of the gastrointestinal unwanted effects of NSAIDs, whilst inhibition of COX-2 results in anti-inflammatory effects. [symbol: see text]Rofecoxib (Vioxx--MSD) and [symbol: see text]celecoxib (Celebrex--Searle) have been developed as selective inhibitors of COX-2. Rofecoxib is licensed for the symptomatic treatment of osteoarthritis, but not for rheumatoid arthritis. The manufacturer claims that "in clinical studies rofecoxib inhibits COX-2 but not COX-1", has "the power of high-dose NSAIDs--diclofenac and ibuprofen" and "superior GI safety profile compared to conventional NSAIDs". Celecoxib is licensed for symptom relief in osteoarthritis and rheumatoid arthritis. The manufacturer claims that celecoxib has "comparable efficacy and superior GI tolerability when compared to diclofenac or naproxen". Here, we review rofecoxib and celecoxib and consider whether they are safer than conventional NSAIDs.     

塞来考昔和布洛芬治疗骨关节炎的比较

目的 :比较塞来考昔和布洛芬治疗骨关节炎的疗效及安全性。方法 :塞来考昔组 34例 ,给予塞来考昔 10 0mg ,po ,bid ;布洛芬组 32例 ,给予布洛芬 30 0mg ,po ,bid ,疗程 4wk。结果 :塞来考昔组的总有效率为 85 % ,布洛芬组为 81% (P >0 .0 5 ) ;2组不良反应发生率分别为 18%和 34% ,2组发生不良反应的病例数差异无显著性。结论 :塞来考昔能改善骨关节炎的症状和体征 ,疗效与布洛芬相近 ,在治疗骨关节炎中可作为非甾体抗炎药的有效替代药物     

Effect of evening primrose oil and ω-3 polyunsaturated fatty acids on the cardiovascular risk of celecoxib in rats

Experimental data raised the specter of increased cardiovascular risk with selective cyclooxygenase-2 inhibitors. The study aimed to investigate the cardiovascular risk caused by celecoxib by studying its effect on blood pressure (BP) and thrombogenesis in rats. We tested the possible protective effects of evening primrose oil (EPO) or ω-3 polyunsaturated fatty acids (n-3 PUFAs). Male Wistar rats were assigned to the following groups: vehicle, celecoxib, celecoxib/n-3 PUFAs, celecoxib/EPO, n-3 PUFAs, and EPO. The rats were treated with celecoxib (20 mg·kg(-1)·d(-1)) by gastric gavage for 6 weeks. The mean BP was recorded, and blood samples were collected for testing prothrombin time and activated partial thromboplastin time. Platelet aggregation assay and collagen-induced platelet consumption test were used as models of thrombogenesis. Celecoxib increased the BP without affecting coagulation parameters and accelerated thrombogenesis by increasing platelet aggregation and collagen-induced thrombocytopenia. EPO and n-3 PUFAs decreased the celecoxib-induced elevation in BP. Although EPO significantly decreased platelet aggregation and collagen-induced thrombocytopenia, n-3 PUFAs did not. Celecoxib elevated BP and increased the risk of thrombogenesis in rats. A combination of celecoxib and the selected natural supplements is suggested as a novel approach to minimize cardiovascular risk caused by celecoxib.     

塞来昔布治疗类风湿关节炎和骨关节炎有效性和安全性的临床研究

目的评价塞来昔布治疗类风湿关节炎(RA)和骨关节炎(OA)的有效性和安全性。方法采用随机、双盲、双模拟和对照研究的方法,将48例患者分为治疗组24例,其中RA14例,OA10例,每天早、晚各服塞来昔布100mg和安慰剂1片;对照组24例,其中RA13例,OA11例,每天早、晚各服双氯芬酸50mg和安慰剂1片,治疗12周以评价药物的安全性和有效性。结果譹两组患者对关节炎疼痛的评估(VAS)均有明显改变;两组差值为3.0,其95%可信区间(CI)为-14.4~20.4;②患者对疾病的总体评价,两组差值为0.1,其95%CI为-0.39~0.59;譻研究者对疾病的总体评价,两组差值为0.05,其95%CI为-0.59~0.49;譼对照组发生胃肠道不良事件3起,治疗组未报告胃肠道不良事件(Fisher精确概率检验,P=0.233)。结论塞来昔布、双氯酚酸均能显著降低患者对关节炎疼痛的评估,改善患者及研究者对疾病状况的总体评价,塞来昔布具有良好耐受性。     

Celecoxib inhibits 5-lipoxygenase

Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor used in the therapy of inflammatory and painful conditions. Various COX-2-independent pharmacological effects, such as a chemo-preventive and tumor-regressive activity have been suggested, but the respective non-COX-2 targets of celecoxib are still a matter of research. We now demonstrate that celecoxib inhibits 5-lipoxygenase (5-LO), a key enzyme in leukotriene (LT) biosynthesis. Celecoxib suppressed 5-LO product formation in ionophore A23187-activated human polymorphonuclear leukocytes (IC(50) approximately 8 microM). Similarly, celecoxib inhibited LTB(4) formation in human whole blood (IC(50) approximately 27.3 microM). Direct interference of 5-LO with celecoxib was visualized by inhibition of enzyme catalysis both in cell homogenates and with purified 5-LO (IC(50) approximately 23.4 and 24.9 microM, respectively). Related lipoxygenases (12-LO and 15-LO) were not affected by celecoxib. Other COX-2 inhibitors (etoricoxib and rofecoxib) or unselective NSAIDs (non-steroidal anti-inflammatory drugs, diclofenac) failed to inhibit 5-LO. In rats which received celecoxib (i.p.), the blood LTB(4) levels were dose-dependently reduced with an ED(50) value approximately 35.2 mg/kg. Together, celecoxib is a direct inhibitor of 5-LO in vitro and in vivo. These findings provide a potential molecular basis for some of the described COX-2-independent pharmacological effects of celecoxib.     

Celecoxib does not affect the antiplatelet activity of aspirin in healthy volunteers

Celecoxib is a novel cyclooxygenase-2-specific inhibitor for the management of acute pain, primary dysmenorrhea, and the signs and symptoms of arthritis. This double-blind, placebo-controlled study in 16 healthy volunteers evaluated whether celecoxib alters the effect of concomitant aspirin on platelet function. Volunteers received celecoxib (400 mg/day) or placebo for 4 days. On day 5, they also received a single 325 mg dose of aspirin with either 200 mg celecoxib or placebo. Thromboxane and platelet aggregation response to adenosine 5'-diphosphate (ADP), collagen, and arachidonic acid were measured before the first dose of celecoxib or placebo (baseline) and before dosing and 2 and 8 hours post dose on day 5. There was no significant difference in thromboxane inhibition between the two groups (percent inhibition: placebo 99.4%, celecoxib 99.0%; p = 0.555). There was also no significant difference in the effect of aspirin on platelet aggregation due to ADP, collagen, or arachidonic acid between the groups. Therefore, these data indicate that celecoxib does not alter the effects of aspirin on platelet function.     

Dyspepsia tolerability from the patients' perspective: a comparison of celecoxib with diclofenac

AIM: To compare celecoxib (800 mg/day, n=1997) with diclofenac (150 mg/day, n=1996) on dyspepsia-related tolerability. METHODS: In one of the two protocols comprising the Celecoxib Long-Term Arthritis Safety Study, a randomized double-blind trial, patients completed the Severity of Dyspepsia Assessment Questionnaire at baseline and at weeks 4, 13, 26 and 52 for the following three scales: Pain Intensity, Non-Pain Symptoms and Satisfaction with Dyspepsia-Related Health. RESULTS: For the Pain Intensity scale, patients given diclofenac had significantly higher (worsening dyspepsia) mean changes, defined as follow-up minus baseline, than patients given celecoxib (P < 0.001, at all assessments). The mean changes in the Pain Intensity scale (scale, 2-47; higher score is higher pain intensity) were 0.99 (95% confidence interval (CI): 0.50, 1.48) for celecoxib and 2.76 (95% CI: 2.28, 3.25) for diclofenac at 4 weeks. Satisfaction was superior with celecoxib at all assessments (P < 0.001). At 4 weeks, the mean changes in the Satisfaction scale (scale, 7-35; higher score is higher satisfaction) were 0.02 (95% CI: - 0.26, 0.29) for celecoxib and - 0.72 (95% CI: - 1.00, - 0.45) for diclofenac. Diclofenac patients had significantly higher Non-Pain Symptoms at 4 weeks (P=0.005). CONCLUSIONS: Celecoxib, at two to four times the recommended dose, demonstrated a superior dyspepsia-related tolerability and satisfaction compared with standard dosages of diclofenac.     

Comparison of the efficacy and tolerability of dexibuprofen and celecoxib in the treatment of osteoarthritis of the hip

CONTEXT: Osteoarthritis (OA) is often treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or selective inhibitors of cyclooxygenase-2 (COX-2). OBJECTIVE: This clinical trial aimed to assess directly the relative therapeutic efficacy of the isolated active enantiomer of ibuprofen, named dexibuprofen (S(+)-ibuprofen) in a special crystal form, and the selective COX-2 inhibitor celecoxib in adults with OA of the hip. Moreover, the hypothesis that the tolerability/safety profile of dexibuprofen is comparable to celecoxib is to be tested. METHODS: The investigation was a randomized, parallel-group, double-blind, active controlled clinical trial, conducted from January 2001 to February 2002 in 4 rehabilitation centers in Austria. 148 inpatients were randomly assigned to dexibuprofen 800 mg or celecoxib 200 mg daily. The primary criterion was the improvement in the Western Ontario and' McMasters osteoarthritis index (WOMAC OA index) after 15 days of therapy. RESULTS: Evaluation of the WOMAC OA index proved that dexibuprofen 400 mg b.i.d. is not inferior to celecoxib 100 mg b.i.d. with the Mann-Whitney estimator equal to 0.5129 and the corresponding lower boundary of the 95% confidence interval equal to 0.4409. The overall incidence of adverse drug reactions was 12.16% in the dexibuprofen group and 13.51% in the celecoxib group. 8.1% of patients on dexibuprofen and 9.5% on celecoxib suffered from gastrointestinal disorders. CONCLUSION: In the presented clinical trial dexibuprofen has at least equal efficacy and a comparable safety/tolerability profile as celecoxib in adult patients suffering from osteoarthritis of the hip.     

Characterization of etoricoxib,a novel,selective COX-2 inhibitor

Etoricoxib is a potent selective COX-2 inhibitor in man. Ex vivo whole-blood assays assessed COX-2 inhibition after oral administration of etoricoxib in single (5-500 mg) and multiple (25-150 mg) once-daily doses to healthy human subjects. A separate study examined ex vivo gastric mucosal PGE2 synthesis after etoricoxib (120 mg qd), naproxen (500 mg bid), or placebo for 5 days. The effect of etoricoxib 120 mg qd on the COX-1-mediated antiplatelet effects of low-dose aspirin (ASA) was also assessed. The mean (time)-weighted average inhibition (WAI) of lipopolysaccharide (LPS)-stimulated PGE2 (COX-2 assay) vcrsus placebo was dose related after single (range: 3.1%-99.1%) and multiple doses (range: 52.5%-96.7%). PGE2 remained significantly inhibited 24 hours postdose at steady state. Inhibition of LPS-stimulated PGE2 showed a strong relationship with etoricoxib plasma concentrations; ex vivo, IC50 was almost identical to in vitro. Multiple dosing of etoricoxib (up to 150 mg qd) showed no important effects on serum TXB2, bleeding time, or platelet aggregation (COX-1-mediated effects). The nonselective nonsteroidal anti-inflammatory (NSAID) naproxen significantly inhibited (approximately 78%) ex vivo prostaglandin synthesis in gastric mucosa; etoricoxib had no effect. Etoricoxib did not interfere with the antiplatelet effects of low-dose ASA, as assessed by serum TXB2 and platelet aggregation. Etoricoxib was generally well tolerated, even at doses above the clinical dose range. Based on these results, etoricoxib is a potent selective inhibitor of COX-2 after single and multiple dosing regimens and does not inhibit prostaglandin synthesis in the gastric mucosa, even at doses above the clinical dose range of 60 to 120 mg.