双氯芬酸钾双层片与普通片在兔体内的生物等效性

Pharmacokinetics of diclofenac potassium double-layer tablets in rabbits and in vitro/in vivo correlations

目的 :研究双氯芬酸钾 (DP)双层片在兔体内的药动学特征。方法 :8只家兔分别单剂量口服DP双层片 (Ⅰ )和普通片凯扶兰 (Ⅱ )各 5 0mg ,采用高效液相色谱法测定不同时间的血药浓度。经TOPFIT程序拟合 ,求算药动学参数。结果 :Ⅰ和Ⅱ的药动力学参数MRT分别为 (19.7± 3 .0 )h和 (7.7± 0 .9)h ,t1 /2 为 (10 .6± 1.1)h和 (3 .2± 1.0 )h ,Tmax为 (8.5± 3 .0 )h和(5 .0± 1.2 )h ,Cmax为 (16.6± 3 .7) μg·ml- 1 和 (2 6.6± 4.1) μg·ml- 1 ,AUC为 (2 66.4± 45 .1) μg·h·ml- 1 和 (92 3 7.0± 19.1) μg·h·ml- 1 。DP双层片和普通片的MRT、t1 /2 、Tmax、Cmax差异有显著性 ,AUC、CL差异无显著性。体内吸收分数与体外释放度之间线性关系良好 ,r =0 .9885。结论 :双层片具有明显的缓释特征 ,吸收程度与普通片等效。

OBJECTIVE To study the pharmacokinetcs of diclofenac potassium double layer tablet (Ⅰ) in rabbits .METHODS A single oral dose of 50mg (Ⅰ)and 50mg odinary tablet kaifulan(Ⅱ) was given to 8 rabbits respectively,drug concentration in plasma was determined by HPLC method.The pharmacokinetics parameters were fitted and caculated by Topfit program.RESULTS The pharmacokinetic parameters of (Ⅰ)and (Ⅱ)were respectively as follows: MRT ( 19.7 ± 3.0 ) and ( 7.7 ± 0.9 ) h, t 1/2 ( 10.6 ± 1.1 ) h and ( 3.2 ± 1.0 ) h, T max ( 8.5 ± 3.0 ) h and ( 5.0 ± 1.2 ) h, C max ( 16.6 ± 3.7 ) μg·ml -1 and ( 26.6 ± 4.1 ) μg·ml -1 ,AUC ( 266.4 ± 45.1 ) μg·h·ml -1 and ( 237.0 ± 19.1 ) μg·h·ml -1 . MRT、 t 1/2 、 T max 、 C max of (Ⅰ)were different from (Ⅱ) significantly. AUC and CL of (Ⅰ) and (Ⅱ) had no significant difference.Correlation between absorption rate in vivo and dissolution rate in vitro was fine( r = 0.9885 ).CONCLUSIONS (Ⅰ) had marked characteristics of sustained release.