痹证1号联合醋氯芬酸钠治疗湿热阻络型急性痛风性关节炎临床研究

目的:评价痹证1号联合醋氯芬酸钠治疗湿热阻络型急性痛风性关节炎的临床疗效。方法:将符合入选标准的160例湿热阻络型急性痛风性关节炎患者采用SAS软件产生的随机数字分为观察组及对照组,每组80例,两组均给予调整生活方式、饮食结构,观察组给予醋氯芬酸钠+痹证1号,对照组给醋氯芬酸钠治疗,均治疗2周。观察两组治疗前后关节肿胀程度、关节压痛评分及血清白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、尿酸(UA)、红细胞沉降率(ESR)变化;采用中医临床标准、尿酸标准评价临床疗效。结果:观察组关节肿胀程度评分治疗后明显低于对照组(P<0.05);观察组关节压痛评分治疗后低于对照组,但无统计学意义(P>0.05);观察组治疗后血清IL-1β、TNF-α、UA、ESR均低于对照组(P<0.05);中医临床疗效总有效率观察组93.2%,对照组87.5%,两组疗效比较差异有统计学意义(P=0.044);UA疗效观察组总有效率92.5%,对照组79.7%,总有效率比较差异有统计学意义(P=0.026)。结论:痹证1号联合醋氯芬酸钠能够有效缓解急性痛风性关节炎关节肿胀、关节压痛的临床症状,未发生不良反应,其机制可能与降低血清IL-1β、TNF-α、UA、ESR水平及减少炎性刺激有关。     

醋氯芬酸片致严重血小板减少1例

1例中年女性患者因手掌和手关节疼痛10月余口服醋氯芬酸片0.1 g,bid,q12h治疗,服药6 d后血小板急剧下降到1.0×109.L-1。本文分析醋氯芬酸片致血小板减少的不良反应发生机制和处理措施,提醒临床医务人员在使用过程中应重视该药潜在的不良反应。     

醋氯芬酸在nano-TiO2/[BnMIM]PF6修饰碳糊电极上的电催化氧化及电分析方法

目的:研究了醋氯芬酸(Aceclofenac,AC)在纳米二氧化钛(nano-TiO2)与离子液体1-苄基-3-甲基咪唑六氟磷酸盐([BnMIM]PF6)复合修饰碳糊电极(nano-TiO2-[BnMIM]PF6/CPE)上的电化学行为和电化学动力学性质,建立了AC电化学定量测定方法。方法:循环伏安法(CV),计时电流法(CA),计时库仑法(CC),方波伏安法(SWV)以及电化学交流阻抗法(EIS)。结果:在nano-TiO2-[BnMIM]PF6/CPE上AC发生了受扩散控制的不可逆电化学氧化过程。测得AC在nano-TiO2-[BnMIM]PF6/CPE上的电极反应过程动力学参数。用SWV法测得AC氧化峰电流与其浓度在5.0×10-5～1.0×10-3mol·L-1呈线性关系,检测限(S/N=3)为1.20×10-7mol·L-1。采用本方法对市售醋氯芬酸片进行了电化学定量测定,RSD在1.9%～3.0%之间,加标回收率在98.6%～103.7%之间。结论:nano-TiO2-[BnMIM]PF6/CPE对AC电化学氧化具有良好的催化作用,该方法可用于市售醋氯芬酸含量的电化学定量测定。     

Pharmacokinetic Interactions Between Eperisone Hydrochloride and Aceclofenac: A Randomized,Open-Label,Crossover Study of Healthy Korean Men

Background

Eperisone hydrochloride, a centrally acting muscle relaxant, is a calcium antagonist that causes vasodilation and antispastic actions. Aceclofenac, an anti-inflammatory analgesic and antipyretic drug, has similar efficacy and improved gastrointestinal tolerance compared with other nonsteroidal anti-inflammatory drugs, such as diclofenac. Although eperisone hydrochloride and aceclofenac are frequently coadministered, no published studies have reported on the pharmacokinetic interactions between these 2 drugs.

Objective

The aim of this study was to investigate any pharmacokinetic interactions between eperisone hydrochloride and aceclofenac in healthy Korean men.

Methods

This was a randomized, open-label, crossover study. Each participant was randomly assigned to 1 of 6 treatment sequences and received eperisone hydrochloride (3 doses of 50 mg each), aceclofenac (2 doses of 100 mg each), or both as a single dose with a 7-day washout period between each dose. Blood samples were collected ≤24 hours after dosing, and plasma eperisone hydrochloride and aceclofenac concentrations were determined using validated LC/MS-MS. Pharmacokinetic analyses were conducted using noncompartmental methods. A safety profile was determined using the measurement of vital signs, ECG, and clinical laboratory tests.

Results

A total 24 of men were enrolled, and all completed the study. The geometric mean ratios (90% CIs) of the C_max and AUC_0-∞ values for eperisone were 1.18 (0.828–1.673) and 1.12 (0.836–1.507), respectively. The geometric mean ratios (90% CIs) of the C_max and AUC_0-∞ for aceclofenac were 0.93 (0.847–1.022) and 1.01 (0.979–1.036), respectively. A total of 7 adverse events were reported in 7 men. All adverse events were mild, and no significant differences were found between treatment groups.

Conclusion

No clinically significant pharmacokinetic differences exist between 150 mg eperisone hydrochloride and 200 mg aceclofenac when administrated as a monotherapy or in combination.     

Drug-induced Sweet’s syndrome by aceclofenac

Sweet’s syndrome (SS) or acute febrile neutrophilic dermatosis is a reactive process that presents in different clinical settings and ranges from classical (idiopathic), malignancy associated or drug induced.

The authors describe a 51-year-old Caucasian woman referred to our department with a 3-day history of pseudovesicular reddish papules on her neck, upper trunk and limbs. Two days prior to the eruption, aceclofenac 100?mg every 8?h was initiated for lower back pain. She also complained of high fever (39°C), arthralgias and general malaise. Laboratory evaluation showed an elevation of erythrocyte sedimentation rate and C reactive protein. A biopsy specimen of skin lesions showed throughout the upper reticular dermis a dense infiltrate of mature neutrophils. Aceclofenac was discontinued and oral prednisolone (0.5?mg/kg) was started. Fever resolved within 48?h, whereas cutaneous lesions cleared within the first week. No relapse was noted after a 6-month follow-up period.

Drug-induced SS by aceclofenac diagnosis was sustained by the presence of all the five diagnostic criteria for drug-induced SS presented by Walker and Cohen in 1996. Several hundred cases of SS have been reported in the literature. However, drug-induced SS represent overall less than 5% of all cases, mostly as isolated clinical cases. Reports of nonsteroidal anti-inflammatory drug-induced SS include diclofenac, celecoxib and rofecoxib. Our patient represents the first case of aceclofenac-induced SS and illustrates the need to enquire about recent drugs in a patient with suspicion of SS.     

Formulation development and optimization of bilayer tablets of aceclofenac

Objective: The objective of the present study was to develop bilayer tablets of aceclofenac that are characterized by initial burst drug release followed by sustained release of drug.

Methods: The fast-release layer of the bilayer tablet was formulated using microcrystaline cellulose (MCC) and HPMC K4M. The amount of HPMC E4M (X₁) and MCC (X₂) was used as independent variables for optimization of sustained release formulation applying 3² factorial design. Three dependent variables were considered: percentage of aceclofenac release at 1 h, percentage of aceclofenac release at 12 h, and time to release 50% of drug (t_50%). The composition of optimum formulation of sustained release tablets were employed to formulate double layer tablets.

Results: The results indicate that X₁ and X₂ significantly affected the release properties of aceclofenac from sustained release formulation. The double layer tablets containing fast-release layer showed an initial burst drug release of more than 30% of its drug content during first 1 h followed by sustained release of the drug for a period of 24 h.

Conclusion: The double layer tablets for aceclofenac can be successfully employed as once-a-day oral-controlled release drug delivery system characterized by initial burst release of aceclofenac for providing the loading dose of drug.     

In Vivo Selectivity of Nonsteroidal Antiinflammatory Drugs and Gastrointestinal Ulcers in Rats

The aim of the present work was to study in vivo COX-2–COX-1 selectivity of 16 nonsteroidal anti-inflammatory drugs (NSAIDs) in equipotent ulcerogenic doses in two in vivo experimental models. Indomethacin, ibuprofen, nimesulide, aceclofenac, aspirin, sodium diclofenac, meloxicam, naproxene, paracetamol, piroxicam, tenoxicam, nabumetone, ketoprofen, mefenamic acid, etodolac, and ketorolac were administered to female Wistar rats (N = 10 each group). In experiment I, solid food plus subcutaneous NSAIDs were given. In experiment II, NSAIDs were given by oral gavage and in bolus. Macroscopic gastric antral ulcer area (30%) and intestinal erosiva area (295 mm2) in experiment I and necrotic gastric fundus area (65%) and erosive intestinal area (182 mm2), in vivo the NSAIDs COX-1 was showed. Neutrofilia assessed in gastric intestinal mucosa where also ibuprofen and paracetamol not given neotrophilic infiltration. In conclusion, COX-2–COX-1 selectivity was demonstrated in vivo with the drugs aceclofenac, nabumetone, meloxicam, nimesulide, and paracetamol.     

Formulation and evaluation of chitosan microspheres of aceclofenac for colon‐targeted drug delivery

The objective of this investigation was to develop novel colon specific drug delivery. Aceclofenac, a NSAID, was successfully encapsulated into chitosan microspheres. Various formulations were prepared by varying the ratio of chitosan, span‐85 and stirring speed and the amount of glutaraldehyde. The SEM study showed that microspheres have smooth surfaces. Microspheres were characterised by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) to confirm the absence of chemical interactions between drug and polymer and to know the formation of microspheres structure. The microspheres were evaluated for particle size, encapsulation efficiency, drug loading capacity, mucoadhesion studies, stability studies, in vitro and in vivo drug release studies. Particle sizes, as measured by the laser light scattering technique, were of an average size in the range 41–80 µm. The swelling index was in the range 0.37–0.82 and the entrapment efficiency range was 51–75% for all the formulations. The optimised batch ACM₁₃ released 83.6% at 8 h and 104% at 24 h in SCF containing rat caecal content. Eudragit coated chitosan microspheres prevented the release of the aceclofenac in the physiological environment of the stomach and small intestine and released 95.9±0.34% in the colon. With regard to release kinetics, the data were best fitted with the Higuchi model and showed zero order release with non‐Fickian diffusion mechanism. The in vivo findings suggest that aceclofenac microspheres exhibit a prolonged effect of aceclofenac in rats and produce a significant anti‐inflammatory effect. The findings of the present study conclusively state that chitosan microspheres are promising for colon targeting of aceclofenac to synchronise with chronobiological symptoms of rheumatoid arthritis. Copyright © 2010 John Wiley & Sons, Ltd.     

醋氯芬酸治疗类风湿性关节炎和骨关炎的临床观察

目的观察醋氯芬酸治疗类风湿性关节炎(RA)和骨关节炎(OA)的疗效和安全性.方法将126名患者随机分为治疗组64例,其中RA36例,OA28例,每天早晚各服醋氯芬酸0.1 g;对照组62例,其中RA35例,OA27例,每天早晚各服布洛芬缓释胶囊0.3 g.疗程均为4周.分别观察治疗前后临床指标和炎性实验的变化以及不良反应的发生.结果醋氯芬酸和布洛芬治疗RA 4周后,疼痛程度,压痛关节数,关节压痛指数,关节肿胀指数,握力,晨僵时间,血沉均显著改善,醋氯芬酸的总有效率为77.8%.两者治疗OA 4周后,膝关节活动痛、15 min行走时间、日常活动能力及患者综合评估均有显著改善,醋氯芬酸的总有效率为71.4%.醋氯芬酸对RA和OA的疗效与布洛芬相比无显著性差异.醋氯芬酸以胃肠道反应为主的不良反应发生率为14.3%,低于布洛芬(25.9%).结论从临床角度而言醋氯芬酸对RA和OA均为安全、有效的治疗药物.