依托考昔联合运动训练治疗膝骨性关节炎临床疗效及作用机制探讨

目的探讨依托考昔联合运动训练治疗膝骨性关节炎(KOA)的临床疗效及作用机制。方法选取2015年2月~2016年9月我院治疗的144例膝骨关节炎患者,采用统计软件SAS9.1程序产生随机分配序列,将其以1∶1∶1∶1的比例被随机分配四组,再实施盲法用A、B、C、D分别表示组别,依托考昔组(A组)、运动训练组(B组)、依托考昔联合运动训练组(C组)和健康教育组(D组)四组,各36例,所有患者均予以KOA常规治疗,A组加以依托考昔治疗,B组加以运动功能训练,C组加以运动训练联合依托考昔治疗,D组进行健康教育,四组患者均治疗12周,比较治疗前后四组患者的骨性关节炎指数评分(WOMAC)、6 min步行距离、SF-36评分及血清炎性因子表达,并记录比较四组患者临床疗效及不良反应的发生情况。结果 (1)A、B、C组治疗后WOMAC评分均低于治疗前,且C组降低更明显(P0.05);(2)A、B、C组治疗后6 min步行距离和SF-36评分均高于治疗前,且C组升高更明显(P0.05);(3)A、B、C组治疗后NF-κB、IL-1β和MMP-1水平均低于治疗前,且C组降低更明显(P0.05);(4)治疗后四组临床总有效率比较存在显著差异,且C组升高更明显(P0.05);(5)四组不良反应发生率比较差异无显著性(P0.05)。结论依托考昔联合功能训练治疗KOA临床疗效显著,可改善患者疼痛及关节运动功能,减少炎性因子表达水平,安全可靠,其机制可能通过调控NF-κB信号通路相关蛋白的表达发挥作用。     

The Biochemical Selectivity of Novel COX-2 Inhibitors in Whole Blood Assays of COX-isozyme Activity

Summary

We have evaluated the biochemical selectivity of novel cyclo-oxygenase (COX)-2 inhibitors, etoricoxib, valdecoxib, DFU and DFP, vs rofecoxib and celecoxib, using the human whole blood assays of COX-isozyme activity, in vitro. Compounds were incubated with human whole blood samples, allowed to clot for 1?h at 37°C, or stimulated with lipopolysaccharide (10|ig/ml) for 24?h at 37°C. Serum thromboxane (TX) B2 and plasma prostaglandin (PG) E2 levels were measured by specific radioimmunoassays as indices of platelet COX-1 and monocyte COX-2 activity, respectively. Valdecoxib, etoricoxib, DFU

and DFP inhibited platelet COX-1 and monocyte COX-2 with the following COX-1/COX-2 IC50 ratios: 61.5, 344, 660 and 1918, respectively. The reference compounds, celecoxib and rofecoxib had corresponding values of 29.6 and 272. In conclusion, a second wave of COX-2 inhibitors with higher biochemical selectivity than the existing coxibs has been developed. Whether their administration will be associated with improved clinical efficacy and/or safety visà-vis celecoxib and rofecoxib remains to be established.     

蚁参蠲痹胶囊联合西药治疗老年类风湿关节炎临床观察

目的观察甲氨蝶呤、依托考昔联合蚁参蠲痹胶囊治疗老年类风湿关节炎的临床疗效。方法将120例老年类风湿关节炎患者随机分为治疗组60例(男性14例、女性46例),对照组60例(男性15例、女性45例)。其中对照组患者口服甲氨蝶呤,每次10 mg,每周1次,口服依托考昔每次60 mg,每天1次。治疗组在对照组基础上加服蚁参蠲痹胶囊每次4粒,每天3次。分别对比观察两组治疗4、8、12周的临床疗效及药物不良反应发生率。结果治疗组临床疗效优于对照组,有显著差别(P0.05)。两组间药物不良反应发生率无显著差别(P0.05)。结论蚁参蠲痹胶囊联合西药治疗老年类风湿关节炎临床疗效显著,且用药安全。     

Computer simulations using GastroPlus™ to justify a biowaiver for etoricoxib solid oral drug products

Purpose

The purpose of this study was to compare the dissolution behaviour of etoricoxib in different dissolution media and to establish in vitro/in vivo correlation (IVIVC) using computer simulations.

Methods

Drug solubility was measured in different media. The dissolution behaviour of etoricoxib was studied in the USP Apparatus 2 using different dissolution media. A dissolution transfer model was used to investigate if the drug stays in solution when the pH of the medium changes. Drug permeability assessment was performed using the caco-2 cell culture technique. The in vitro data were used as input functions in GastroPlus™ to simulate the in vivo profiles of the drug.

Results

Solubility of etoricoxib was highest at low pH, and there was no significant difference in the solubility observed between blank buffers and biorelevant media of similar pH. The drug remained solubilised when transferred into simulated intestinal fluids. Using the in vitro data as input function in Gastro Plus, an IVIVC was established. Further simulations confirmed that the drug absorption occurs similar to the absorption of an oral solution.

Conclusions

Due to the solubility behaviour within the physiological pH gradient of the gastrointestinal tract, etoricoxib can be classified as an intermediate class 1/2 drug rather than BCS class 2. In vitro results combined with in silico simulations using GastroPlus support scientifically that a biowaiver for immediate release etoricoxib solid oral dosage forms is justified.     

Evaluation of quality of life following treatment with etoricoxib in patients with arthritis or low-back pain: an open label,uncontrolled pilot study in Mexico

An open-label study was undertaken at multiple centers in Mexico to assess the impact of treatment with etoricoxib - a selective cyclo-oxygenase-2 (COX-2) inhibitor - on quality of life (QoL) and pain relief among patients with osteoarthritis (OA), rheumatoid arthritis (RA) or chronic low-back pain (CLBP). The study involved 191 adult patients (aged > 18years old) who had used non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of OA, RA or CLBP during the month prior to study enrolment. After discontinuation of prior therapy, patients were treated with etoricoxib 60?mg for OA and CLBP, or 90?mg for RA once daily for 2 weeks.

Patient and physician questionnaires were used to collect information about drug treatments, patients' QoL (Short Form-8 Health Survey [SF-8?] and EQ-5D VAS), patients' pain assessment, and physicians' and patients' satisfaction with treatment at baseline and at follow-up visits.

Relative to prior NSAID use, etoricoxib use was associated with improvements in all SF-8 QoL domains and component scores as well as in measures of pain and physical functioning. Current pain was reduced from 59.1?mm (0-100mm VAS) at baseline to 27.1?mm at follow-up and the physical component score of the SF-8 improved from 33.3 to 46.3 (on a scale from 0 to100). At follow-up, 91% of patients were satisfied with the pain control provided by etoricoxib compared with 34% who were satisfied with the pain control provided by previous NSAIDs. Among physicians, 93% reported satisfaction with the analgesic effect, 95% with the anti-inflammatory profile, and 82% with the side-effect profile of etoricoxib relative to pre-study NSAID treatment. During etoricoxib therapy, use of concomitant medications was reduced.

The results of this study are limited due to the lack of a control group, the un-blinded design, and the small number of patients. Large naturalistic trials are needed to confirm the results.     

Etoricoxib versus naproxen in patients with rheumatoid arthritis: a prospective,randomized, comparator-controlled 121-week trial

ABSTRACT

Background: Etoricoxib is a cyclooxygenase-2 (COX?2) selective inhibitor effective in the treatment of rheumatoid arthritis. An initial 12-week treatment study found that etoricoxib (90?mg once daily) was more effective than naproxen (500?mg twice daily) or placebo in treating rheumatoid arthritis. The present two-part extension of that study was performed to monitor tolerability and examine long-term efficacy of etoricoxib 90?mg or 120?mg compared with naproxen.

Methods: Patients completing the initial 12-week study and those discontinuing due to lack of efficacy, were eligible for the Extension Study Part I (12–52 weeks) and assigned (2?:?1?:?2 ratio) to receive etoricoxib (90?mg or 120?mg daily) or naproxen (500?mg twice daily); these patients remained on the same therapy for Extension Study Part II (52–121 weeks). Primary outcome measures included investigator and patient assessment of disease activity, and tender and swollen joint counts.

Results: Of 816 patients enrolled in the initial 12-week trial, 717 continued into the Extension Study Part I; 505 patients completed and 390 entered the Extension Study Part II, with 283 patients completing 121 weeks. Patients receiving etoricoxib (90?mg) or naproxen throughout the study experienced sustained efficacy in all outcomes, as did patients transitioning to etoricoxib (120?mg) following the initial 12-week trial. Patients transitioning from placebo to etoricoxib (90?mg) experienced rapid, sustained improvements in all outcome measures.

Conclusion: In conclusion, etoricoxib provided sustained efficacy throughout the 121-week study, with efficacy comparable to naproxen.     

Synthesis,characterizations, in vitro and in vivo evaluation of Etoricoxib-loaded Poly (Caprolactone) microparticles – a potential Intra-articular drug delivery system for the treatment of Osteoarthritis

Intra-articular Drug delivery systems (IA-DDS) deliver the drug directly to the diseased joint space with significantly lowered systemic toxicities. In this work, we explored Etoricoxib (COX-2 inhibitor)-loaded Poly caprolactone (PCL) microparticles (MPs) as a potential IA-DDS. MPs were prepared by Oil/Water (O/W) emulsion-solvent evaporation method. Formulation parameters like polymer to drug ratio, stabilizer concentration were optimized to get the maximum encapsulation efficiency. The prepared particles were characterized using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction studies (XRD), and Differential Scanning Calorimetry (DSC). The particles were found to be spherical and smooth-surfaced using SEM. FTIR studies proved that there was no chemical interaction between the drug and the polymer. XRD and DSC studies confirmed that Etoricoxib existed in its amorphous form while PCL had retained its semi-crystalline phase during the micro-encapsulation process. In vitro drug release studies proved that there was controlled release of the drug from the MPs for nearly 28 days. In vivo synovial drug clearance studies on SD rats proved that drug leach out rate from the joint region to the systemic circulation was slow which indicated that MPs had a good drug retention capacity. In vivo fluorescence imaging results confirmed that MPs could stay longer in the joint region for almost a month. Thus, PCL microparticles could be a potential IA-DDS for the treatment of the diseased joint regions especially for Osteoarthritis.     

依托考昔和美洛昔康治疗急性痛风的临床效果以及安全性分析

目的比较依托考昔与美洛昔康治疗急性痛风的临床效果及其用药安全性。方法选择2010年1月-2013年1月本院收治的急性痛风患者120例为研究对象,随机分为依托考昔组及美洛昔康组,每组60例。依托考昔组服用依托考昔120 mg/d,美洛昔康组服用美洛昔康15 mg/d,测定患者疼痛的自我评分并记录药物不良反应。结果治疗后,两组患者的疼痛评分均下降,且依托考昔组的疼痛改善情况明显优于美洛昔康组（P〈0.05）。依托考昔组不良反应发生率为30.0%,美洛昔康组不良反应发生率为33.3%,两组差异无统计学意义（P〉0.05）。结论依托考昔治疗急性痛风的临床效果优于美洛昔康。