双嘧达莫缓释微丸的药动学及相对生物利用度研究

Studies on pharmacokinetics and relative bioavailability of dipyridamole sustained release pellets

目的 :以市售双嘧达莫普通片为参比制剂 ,评价自制双嘧达莫缓释微丸的相对生物利用度和生物等效性。方法 :采用随机交叉分组实验设计 ,给 4条Beagle犬分别给予单剂量 5 0mg的双嘧达莫缓释微丸和普通片 ,po ,按设计采集 12h内动态血标本 ;以经改进的HPLC法测定血浆药物浓度 ,以二室模型计算 2种制剂在动物体内的药动学参数和相对生物利用度。结果 :参比制剂和测试制剂的Tmax 分别为 (0 .92± 0 .0 9)h和 (1.5 7± 0 .12 )h ,Cmax分别为 (434.4± 36 .93)ng·mL- 1 和 (2 79.5 2± 2 4 .8)ng·mL- 1 ,AUC0～ 1 2 分别为 (92 2 .5 6± 5 2 .73)ng·h·mL- 1 和(115 2 .87± 5 5 .18)ng·h·mL- 1 ,t1 2 α分别为 (0 .6 9± 0 .0 5 )h和 (0 .89± 0 .12 )h ,t1 2 β分别为 (4.71± 0 .71)h和(17.6± 5 .5 3)h ,MRT分别为 (2 .91± 0 .14 )h和 (3.5 4± 0 .0 6 )h ,统计分析显示 ,各主要药动学参数均有显著性差异。双嘧达莫缓释微丸相对于普通片的平均生物利用度为 (12 5 .0 6± 4 .38) %。结论 :双嘧达莫缓释微丸具有明显的缓释特征 ,其生物利用度和药物吸收程度显著优于双嘧达莫普通片。

Objective:To study the relative bioavailability and bioequivalence of dipyridamole(DIP) sustained release pellets in Beagle dogs.Methods:A rapid and sensitive RP HPLC assay was modified for the determination of the drug levels in plasma.In a randomized two way crossover design,50mg single dose po DIP common tablets and sustained release pellets,respectively,were given to 4 male Beagle dogs.The parameters were estimated by two compartment model with a statistic analysis of ANOVA.Results:The T max , C max , AUC 0～12 , t 1/2 α, t 1/2 β and MRT of DIP common tablets and sustained release pellets were(0.92±0.09)h and(1.57±0.12)h,(434.4±36.93)ng·mL -1 and (279.52± 24.8)ng·mL -1 ,(922.56±52.73)ng·h·mL -1 and (1 152.87±55.18)ng·h·mL -1 , (0.69± 0.05)h and (0.89±0.12)h,(4.71±0.71)h and (17.6±5.53)h,(2.91±0.14)h and (3.54± 0.06)h,respectively.The mean relative bioavailability of the DIP sustained release pellets vs common tablets was (125.06±4.38)%.Conclusion:The results suggested that the DIP sustained release pellets were more excellent in bioavailability and absorption than common tablets.