国产双氯芬酸钠缓释栓与普通栓的生物等效性  

Bioequivalence study of diclofenac sodium sustained released suppository in Chinese healthy volunteers

作　　者：胡爱萍[1] 胡国新[1] 邱相君[1] 代宗顺[2] 

机构地区：[1]温州医学院药理学教研室,温州325027 [2]华中科技大学同济医学院临床药理学教研室,武汉430030

出　　处：《中国临床药学杂志》2004年第5期273-277,共5页Chinese Journal of Clinical Pharmacy

摘　　要：目的 :研究国产双氯芬酸钠缓释栓和普通栓的生物等效性。方法 :2 0名健康志愿者随机分成 2组 ,采用双周期交叉试验设计 ,单剂量 (10 0mg)或多剂量连续给药 ,用HPLC法测定血浆中双氯芬酸钠的血药浓度。结果 :缓释栓和普通栓的主要药动学参数分别如下 :单剂量cmax为 (1 0 87± 0 2 98)、(1 2 0 2± 0 4 11)mg·L-1;tmax为 (1 6 92± 0 6 6 5 )、(1 10 8± 0 4 30 )h ;AUC0 -12为 (3 770± 1 2 2 3)、(3 2 34± 0 737)mg·h·L-1;T1/ 2 (ke) 为 (2 346± 0 5 77)、(2 132± 0 6 99)h ;平均相对生物利用度F0 -12 为(115 5± 19 8) %。多剂量cmax分别为 (1 370± 0 315 )、(1 6 4 1± 0 5 18)mg·L-1;cmin为 (0 10 3± 0 0 32 )、(0 0 76± 0 0 35 )mg·L-1;tmax为 (2 175± 0 6 5 4 )、(1 4 5 8± 0 4 5 8)h ;AUC0 -12 为 (5 4 5 9± 1 2 78)、(5 2 99± 0 96 4 )mg·h·L-1;血药浓度的波动度分别为(2 79 4 35± 4 7 0 4 1) %、(347 195± 71 6 5 5 ) %。经方差分析和双单侧t检验 ,2种制剂间AUC无显著性差异 (P >0 0 5 ) ;tmax(P <0 0 5 ) ,缓释栓达峰时间明显延长 ;多剂量缓释栓cmax小于普通栓 (P <0 0 5 )。结论 :2种制剂具有生物等效性 。AIM: To study the boiequivalence between diclofenac sodium sustained-released suppository and normal one in healthy volunteers. METHODS: Twenty healthy volunteers were randomly devided into 2 groups. Double-periodical crossed design was used, and poly-dose of diclofenac sodium was administered to 20 volunteers following single-dose(100 mg) after two-weeks interval. The concentrations of diclofenac sodium in plasma were determined by HPLC. The relative boiavailability and related parameters of pharmacokinetics were calculated by 3P97 program, and the bioequivalance between sustained-released suppository of diclofenac sodium and normal one were veritied. RESULTS: The main pharmacokinetic parameters of 2 formulations, sustained-released suppository and normal one, were as follows: In the single-dose test, the c max of the test and reference were (1.087±0.298) and (1.202±0.411)mg·L -1; t max were (1.692±0.665) and (1.108±0.430)h respectively; AUC 0-12 were(3.770±1.223) and (3.234±0.737)mg·h·L -1; T 1/2(ke) were(2.346±0.577) and (2.132±0.699)h; The bioavailability of the test drug was (115.5±19.8)%. In the poly-dose test, the c max were (1.370±0.315) and (1.641±0.518)mg·L -1;c min were (0.103±0.032) and (0.076±0.035)mg·L -1;t max were (2.175±0.654) and (1.458±0.458)h;AUC 0-12 were (5.459±1.278) and (5.299±0.964)mg·h·L -1; DF were (279.435±47.041)% and (347.195±71.655)%. The main pharmacokinetic parameters between the 2 formulations had no significant difference(P>0.05),except t max and c max. CONCLUSION: The 2 formulations are bioequivalent, and the sustained-released suppository is credible.

关 键 词：双氯芬酸钠 生物等效性 缓释 多剂量 单剂量 血药浓度 AUC 国产 平均 目的 

分 类 号：R96[医药卫生—药理学]