复方丹参膜控缓释片与复方丹参片在Beagle犬体内的药动学及生物利用度的比较研究

Comparison of Bioavailability and Pharmacokinetic Study between Fufang Danshen Tablets and Fufang Danshen Sustained Release Tablets in Beagle Dogs

目的了解复方丹参膜控缓释片在Beagle犬体内的药动学行为和生物等效性。方法以丹参酚酸B为指标性成分,比较复方丹参缓释片与复方丹参片单次给药及多次给药达稳态后在Beagle犬体内的药动学参数。结果 Beagle犬口服复方丹参膜控缓释片后,丹参酚酸B的体内动力学过程符合单室模型,与连续3次服用复方丹参片相比,Beagle犬单剂量口服复方丹参缓释片最大血药浓度由1.668μg/mL降至0.973μg/mL,达峰时间由29.428 min后移至81.179 min,消除半衰期从29.383 min延长至261.745 min;多次口服复方丹参膜控缓释片与复方丹参片达稳态后,两者最大血药浓度分别为2.108μg/mL与3.100μg/mL,达峰时间分别为83.080min与21.418 min,消除半衰期分别为219.625 min与21.802 min;Beagle犬单剂量口服复方丹参膜控缓释片的相对生物利用度为89.9%;而多次口服复方丹参膜控缓释片与复方丹参片达稳态后两者相对生物利用度为93.6%;结论本实验的复方丹参缓释片具有良好的缓释效果。

Objective To observe the pharmacokinetic behavior of Fufang Danshen sustained release tablets in Beagle dogs.Methods The differences of the pharmacokinetic parameters among the Fufang Danshen sustained release tablets in Beagle dog were compared,with Salvianolic acid B was used as the main study compound. Results The Danshen sustainedrelease tablets in vivo study showed the Salvianolic acid B fit the single compartment model. After 3 times administration of the Fufang Danshen tablets,the maximum plasma concentration was 1. 668 μg /mL,peak time was 29. 428 min and the t1 /2was 29. 383 min. After administration of single dose of Fufang Danshen sustained-release tablets,the maximum plasma concentration was 0. 973 μg /mL,peak time was 81. 179 min and the t1 /2was 261. 745 min. After multi-administration of the Fufang Danshen sustained-release tablets and Fufang Danshen tablets till the steady state,the maximum plasma concentration was 2. 108 μg /mL and 3. 100 μg /mL,respectively; peak time was 83. 080 min and 21. 418 min respectively; and the t1 /2was 219. 625 min and 21. 802 min. Compared with three times administration of the Fufang Danshen tablets,the relative bioavailability of a single dose of Danshen sustained-release tablets was 89. 9% after oral administration; while the multiple Danshen sustained-release tablets and Fufang Danshen tablets till the steady state the relative bioavailability was 93. 6%. Conclusion The studies show that Danshen sustained-release tablets have a good sustained-release profile.