论文部分内容阅读
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 evaluate the relative bioavailability and bioequivalence of homemade dipyridamole sustained-release pellets with the reference tablets of commercial dipyridamole. METHODS: Four Beagle dogs were given a single dose of 50 mg of dipyridamole sustained-release pellets and normal tablets, respectively, using a randomized crossover design. The dynamic blood samples were collected within 12 hours according to the design. Plasma drug concentration, two-compartment model was used to calculate the pharmacokinetic parameters and relative bioavailability of two formulations in animals. Results: The Tmax of the reference preparation and the test preparation were (0.92 ± 0.99) h and (1.57 ± 0.12) h respectively, and the Cmax were (434.4 ± 36.93) ng · mL-1 and (2 79.5 2 ± 2 4 .8) ng · mL-1, and the AUC0 ~ 1 2 were (92 2 .5 6 ± 5 2 .73) ng · h · mL-1 and (115 2 .87 ± 5 5 .18) ng · h · mL-1, t1 2 α were (0.69 ± 0.05) h and (0.89 ± 0.12) h respectively, t1 2 β were (4.71 ± 0. 71) h and (17.6 ± 5.53) h, MRT were (2.91 ± 0.14) h and (3.54 ± 0.06) h respectively. Statistical analysis showed that all the major pharmacokinetic parameters There are significant differences. The average bioavailability of dipyridamole sustained-release pellets relative to conventional tablets was (12.56 ± 4.38)%. Conclusion: The dipyridamole sustained-release pellets have obvious sustained-release characteristics, and their bioavailability and drug absorption are significantly better than that of dipyridamole common tablets.