双氯芬酸钾的人体药代动力学特点研究

采用反相高效液相色谱法测定双氯芬酸钾盐的血浆药物浓度,通过与双氯芬酸钠比较,研究双氯芬酸钾粉剂在人体内药动学过程的特点。结果表明,双氯芬酸钾与双氯芬酸钠在吸收速度及程度方面相比,双氯芬酸钾有较稳定的吸收过程,Tmax及AUC值的个体差异较双氯芬酸钠小(变异系数小)。受试者口服双氯芬酸钠无明显双峰曲线现象。提示双氯芬酸钾的体内吸收过程较双氯芬酸钠有一定的优点。     

双氯芬酸钾的人体药代动力学特点研究

采用反相高效液相色谱法测定双氯芬酸钾盐的血浆药物浓度,通过与双氯芬酸钠比较,研究双氯芬酸钾粉剂在人体内药动学过程的特点。结果表明,双氯芬酸钾与双氯芬酸钠在吸收速率及程度方面相比,双氯芬酸钾有较稳定的吸收过程,Tmax及AUC值的个体差异较双氯芬酸钠小（变异系数小）。受试者口服双氯芬酸钠无明显双峰曲线现象,提示双氯芬酸钾的体内吸收过程较双氯芬酸钠有一定的优点。     

丁香挥发油与氮酮对双氯芬酸钠促透作用的比较研究

目的:比较丁香挥发油与氮酮对双氯芬酸钠的促透作用。方法:在体外透皮吸收装置上,测定不同时间双氯芬酸钠的透过量,计算稳态流量和增渗倍数,并考察其储库效应。结果:丁香挥发油和氮酮均有促进双氯芬酸钠经皮渗透的作用,当二者合用时效果更显著。丁香挥发油与氮酮单用及合用时对双氯芬酸钠的储库效应均有显著的增强作用(P<0.05或P<0.01)。结论:丁香挥发油对双氯芬酸钠具有较强大的促透作用,可望开发成为一种透皮吸收促进剂。     

功效函数法评价双氯芬酸钠的透皮吸收效果

目的:探讨功效函数法在药物透皮吸收研究中的应用。方法:以双氯芬酸钠为模型药物,BALB/c裸小鼠、KM小鼠、SD大鼠及小型猪的腹部、背部、耳背部皮肤为载体,双氯芬酸钠稳态流量、渗透系数和滞后时间为指标,在双室透皮扩散装置上,通过离体动物皮肤渗透释药实验,采用功效函数法进行多指标综合评价。结果:双氯芬酸钠在不同动物不同部位皮肤中的渗透效果不同,以双氯芬酸钠在BALB/c裸小鼠背部皮肤上的透皮吸收效果最好。结论:功效函数法能够比较客观、合理地评价药物的透皮吸收效果。     

在裸小鼠皮肤上松节油对双氯芬酸钠的渗透动力学研究

目的以双氯芬酸钠为模型药物,研究松节油对药物的透皮吸收促透作用.方法采用氮酮、松节油对皮肤预处理的方法,通过离体裸小鼠皮肤渗透释药实验,不同时间取样,测定接受液中双氯芬酸钠的浓度,计算累积透过量、稳态流量、渗透系数和滞后时间等指标.结果松节油对双氯芬酸钠促透作用较氮酮弱,但其时滞较氮酮短(P<0.05).两种促透剂均减弱双氯芬酸钠的储库效应,其中松节油减弱程度没有氮酮大;两种促透剂对双氯芬酸钠的时滞均有延长,松节油延长更明显(P<0.05).结论松节油对双氯芬酸钠有一定的促透作用.     

广藿香挥发油对双氯芬酸钠经皮渗透动力学研究

目的以双氯芬酸钠为模型药物,研究广藿香挥发油对药物透皮吸收的促进作用。方法采用氮酮、广藿香挥发油预处理皮肤的方法,通过离体大鼠皮肤渗透释药试验,在不同时间点取样,测定接受液中双氯芬酸钠的浓度,计算累积透过量、稳态流量、渗透系数和滞后时间等指标。结果广藿香挥发油对双氯芬酸钠有促透作用,广藿香挥发油组和氮酮组的促渗作用差异有统计学意义(P0.05),但比氮酮的弱;挥发油组可延长双氯芬酸钠的时滞,而氮酮组缩短双氯芬酸钠的时滞;透皮实验中,二者并未减弱双氯芬酸钠的贮库效应;去角质层实验中,二者均减弱了双氯芬酸钠的贮库效应。结论广藿香挥发油对双氯芬酸钠有一定的透皮吸收促进作用。     

双氯芬酸钠(奥尔芬)缓释颗粒胶囊的临床应用

<正> 双氯芬酸钠以不同的途径治疗各种急、慢性疼痛和炎症等。 1.药理机制:双氯芬酸钠为一种新型的强效消炎镇痛药,具有抑制前列腺素的合成,并有阻止血小板凝聚的作用,因此适用于治疗风湿或风湿性炎症和疼痛,其镇痛消炎及解热作用比乙酰水杨酸强20至50倍。特点为药效强,不良反应少,剂量小,个体差异小,口服吸收迅速,服用1至2小时血液浓度达峰值、排泄快,长期服用无蓄积作用。双氯芬酸钠缓释     

HPLC法测定复方双氯芬酸钠注射液中双氯芬酸钠和盐酸利多卡因的含量

复方双氯芬酸钠注射液为一消炎镇痛药,每2mL含双氯芬酸钠75 mg、盐酸利多卡因20 mg及辅料丙二醇、乙酰半胱氨酸、依地酸二钠、聚乙二醇、氢氧化钠等。有关双氯芬酸钠及盐酸利多卡因的测定,中国药典均有收载。复方双氯芬酸钠注射液的厂附质量标准采用紫外分光光度法测定双氯芬酸钠,气相色谱法测定盐酸利多卡因,该法较     

双氯芬酸钠人血浆蛋白结合率的测定

双氯芬酸钠是一种常用的非甾体类抗炎药．具有疗效确切、不良反应小等特点,在临床上有很好的应用跚。本实验建立了双氯芬酸钠在人血浆及在透析液中的含量分析方法,结合平衡透析法考察了双氯芬酸钠人血浆蛋白结合率。为临床上双氯芬酸钠的血药浓度监测和应用提供方法和依据。     

双氯芬酸钾水凝胶的制备和质量评价

目的研制双氯芬酸钾水凝胶．并对其进行质量评价。方法用卡波姆940为基质．用紫外分光光度法测定制剂中双氯芬酸钾的含量．并建立制剂的其他质量评价指标。结果双氯芬酸钾在277nm处有最大吸收．而且基质几乎无干扰，浓度在2～20μg·mL^-1范围内，呈良好线性关系。结论该凝胶制剂制备简单，稳定悼好，刺激性小，质量控制方法简便易行，定量准确。     

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     

双氯芬酸钾胶囊人体药代动力学与相对生物利用度研究

目的 :研究双氯芬酸钾胶囊在正常人体内的药代动力学与相对生物利用度。方法 :采用HPLC法测定10名健康男性志愿者随机自身交叉单剂量口服50mg 双氯芬酸钾胶囊和进口双氯芬酸钾片后的血药浓度 ,计算两者的药代动力学参数及相对生物利用度 ,并以AUC(0～6) 、Tmax 、Cmax 为指标 ,用配对t检验法分析国产胶囊与进口片的生物等效性。结果 :国产与进口双氯芬酸钾制剂的药 -时曲线符合口服吸收一房室模型。AUC(0～6 ) 分别为 (1834 52±711 06) μg/(h·L)、(1891 19±859 08) μg/(h·L) ;Tmax 分别为 (1 15±0 77)h、(1 30±0 97)h ;Cmax 分别为 (1522 29±1063 87)ng/ml、(1508 54±892 44)ng/ml。配对t检验结果表明 ,AUC(0～6) Tmax、Cmax 均无显著性差异 (P>0 05)。结论 :国产双氯芬酸钾胶囊对进口片的相对生物利用度为 (100 80±16 59) % ,国产与进口两种双氯芬酸钾制剂具有生物等效性     

Pharmacokinetic comparison of an oral diclofenac potassium liquid-filled soft gelatin capsule with a diclofenac potassium tablet

Objective: To compare the pharmacokinetic profiles of diclofenac potassium liquid-filled soft gelatin capsules (DPSGC) using patented ProSorb^® dispersion technology with an immediate-release, diclofenac potassium 50-mg comparator tablet in two open-label, single-dose, randomized, crossover relative bioavailability studies in healthy volunteers. Methods: In Study 1, volunteers (n = 21) received DPSGC 50 mg or a diclofenac potassium 50-mg comparator tablet in two inpatient study periods. In Study 2 (n = 54), volunteers received DPSGC 25 mg, DPSGC 50 mg, or a diclofenac potassium 50-mg comparator immediate-release tablet in three inpatient study periods. Results: In both studies, DPSGC 50 mg displayed a significantly shorter T_max and higher C_max than the 50-mg diclofenac potassium comparator tablet. DPSGC 25 mg (Study 2) produced a shorter T_max (0.45 h) and an equivalent C_max (1125 ng/ml) to the 50-mg comparator drug. Plasma diclofenac concentration–time courses for the diclofenac potassium 50-mg comparator tablet showed many low, delayed, or multiple peaks compared with DPSGC treatments. Conclusions: DPSGC 25 mg and 50 mg were more rapidly and consistently absorbed than diclofenac potassium 50-mg comparator tablets. The C_max of DPSGC 25 mg was equivalent to the 50-mg diclofenac potassium comparator tablet. These characteristics may be beneficial when fast, consistent drug absorption is needed.     

Pharmacokinetics of diclofenac after oral administration of its potassium salt in sachet and tablet formulations

This paper reports the results of a pharmacokinetic study involving 24 healthy volunteers and designed to characterise the rate and extent of diclofenac absorption after the administration of a single dose of diclofenac (CAS 15307-86-5) potassium salt 50 mg in sachet (Voltfast) and tablet (Cataflam) formulations. Timed plasma concentrations of diclofenac during a 12-h-period after dosing were measured by means of HPLC with UV detection at 275 nm and a quantification limit of 10 ng/ml; the method was fully validated for pharmacokinetic purposes. These plasma concentrations were used to calculate Cmax, tmax, trapezoidal AUC0-t and AUC0-infinity and t1/2 by means of noncompartmental analysis. Cmax and tmax are the parameters expressing the rate of absorption, whereas the AUCs reflect the extent of absorption. The rate of absorption with the sachets proved to be very fast, reaching peak values at 10 min in seven subjects and at 15 min in the remaining subjects: mean time was 13.68 min, with concentrations at 5 min being 38% of Cmax. The average time to peak concentration with the tablets was 53.10 min. The extent of absorption of the sachets and tablets was similar, with AUC0-infinity values of respectively 1362 and 1214 ng.ml-1.h, and a 90% confidence interval 1.05-1.20. The highly soluble potassium salt of diclofenac was rapidly absorbed, especially in its sachet formulation, and thus appears to be an invaluable analgesic agent that is particularly useful for quick pain relief.     

The pharmacokinetics of diclofenac sodium in patients with active rheumatoid disease

Summary Pharmacokinetic data for diclofenac sodium has been well established in healthy volunteers, whereas in patients with rheumatoid arthritis very little information is available in the literature. A single oral dose of enteric-coated diclofenac sodium was given to 10 patients with active rheumatoid disease, adopting the same procedures used for a group of 10 healthy volunteers in whom pharmacokinetic data was already available. Plasma specimens were collected over a period of 8h following administration and concentrations of diclofenac determined by GLC. Resulting plasma concentration curves were similar to those obtained in the healthy subjects in that areas under curves and terminal half-lives were comparable. However, peak concentrations of diclofenac were significantly reduced in the rheumatoid patients. The lower peak concentrations were correlated with the lower serum albumin levels in the patients which are associated with active rheumatoid disease.     

双氯酚酸钾胶囊剂正常人体生物等效性研究

8名健康男性志愿者自身交叉单剂量口服双氯酚酸钾 5 0mg胶囊剂和片剂 ,采用反相高效液相色谱法测定经时过程血药浓度 .其数据用 3P87程序拟合 ,两制剂的血药浓度 -时间曲线符合单室模型特征 ,求得双氯酚酸钾胶囊剂和片剂的药动学参数 :ka分别为 (1 5 83± 0 2 19)和(1 417± 0 171)h-1;t1/2 分别为 (2 34 8± 0 5 48)和 (2 2 48± 0 5 5 8)h ;Cmax分别为 (1 35 3± 0 2 45 )和 (1 2 37± 0 2 90 ) μg/mL ;Tmax分别为 (1 0 6 1± 0 174)和 (1 2 0 5± 0 2 0 3)h ;AUC分别为 (4 117±1 137)和 (4 131± 0 983) (μg·h) /mL .经统计学处理 :两制剂的药动学参数无显著性差异(P >0 0 5 ) ,双氯酚酸钾胶囊剂相对于片剂的生物利用度F为 (99 6 6± 7 80 ) % .经方差分析 ,双单侧t检验分析 ,证明两制剂具有生物等效性     

双氯芬酸钠缓释片在健康人体的药代动力学和生物等效性

目的:评价双氯芬酸钠缓释片受试制剂和参比制剂在健康人体的药代动力学和生物等效性。方法:24例健康男性志愿者分别行单剂量和多剂量交叉口服双氯芬酸钠缓释片受试与参比制剂,用高效液相色谱-串联质谱法测定血浆中双氯芬酸钠的血药浓度,计算药代动力学参数及相对生物利用度。结果:单剂量口服受试制剂和参比制剂的主要药动学参数如下:Cmax分别为(568.38±271.26)和(458.64±173.96)ng.mL-1,Tmax分别为5(0.5,12)和1.5(0.5,7)h,AUC0～24 h分别为(2 557.72±659.43)和(2 364.14±698.08)ng.h.mL-1,AUC0～∞分别为(2 655.25±635.48)和(2 843.62±808.61)ng.h.mL-1,MRT分别为(6.3±1.8)和(7.0±1.7)h;多剂量口服受试制剂和参比制剂的主要药代动力学参数为:T(ss,max)分别为5(1,7)和4(0.5,8)h,C(ss,max)分别为(520.58±245.89)和(522.98±234.36)ng.mL-1,C(ss,min)分别为(24.96±20.79)和(22.68±17...     

Pharmacokinetic Analysis of the Absorption Characteristics of Diclofenac Sodium in Man by use of a Multi-segment Absorption Model

The pharmacokinetic analysis of an oral sustained-release preparation of diclofenac sodium has been investigated using multi-segment absorption models in which it has been assumed that the gastrointestinal tract can be divided into several segments in each of which the drug has its own lag-time and absorption rate constants. Plasma concentration-time data for sustained release diclofenac sodium in man were fitted both by a conventional pharmacokinetic method assuming first-order absorption and by a multi-segment absorption model. The plasma concentration of diclofenac sodium calculated on the basis of the multi-segment absorption model was found to correlate with the observed plasma concentration. It was concluded that diclofenac sodium data can be better described by a multi-segment absorption model than by a conventional pharmacokinetic model. The results also show that multi-segment absorption models are suitable for pharmacokinetic analysis of plasma drug-concentration data with irregular or multiple peaks in the absorption profiles, and also for the pharmacokinetic analysis of sustained-release preparations.     

A study to determine the clinical relevance of the pharmacokinetic interaction between aspirin and diclofenac

Interaction studies in the rat and healthy human volunteers have shown that protein binding of diclofenac is reduced by the addition of salicylic acid causing an increased free drug level of diclofenac. The diclofenac area under curve (AUC) is also reduced by approximately one-third in the presence of salicylate. We have performed a crossover comparison of soluble aspirin, diclofenac and the two drugs in combination in patients with rheumatoid arthritis to determine whether this had clinical relevance. 36 patients entered the study. There was a high dropout rate on aspirin alone but analysis of completors (22 patients) showed diclofenac either alone or in combination to be superior to aspirin alone on two of the five clinical parameters measured. There was no significant difference between disclofenac and aspirin + diclofenac. We thus found no clinical manifestations of the pharmacokinetic interaction.     

双氯芬酸钾凝胶剂的制备及抗炎作用研究

以双氯芬酸钾为主药,利用卡波姆溶液在pH6～12可胶凝成稳定的凝胶原理,制备具有水溶性半固体凝胶剂。采用高效液相色谱法进行含量测定,平均回收率为99．55％,RSD为1.22％。研究表明该制剂的配制及质控方法可行,与进口同类制剂产品进行动物抗炎疗效比较,抗炎作用显。