心宁缓释片在犬体内的药动学-药效学研究

Study on Pharmacokinetics-Pharmacodynamics of Xinning Extended Action Tablet on Dogs

目的:应用药动学-药效学研究相结合的方法探讨心宁缓释片在犬体内的量效关系,并评价其在体内的缓释效果。方法:将60只杂种犬冠脉结扎后,观察其经食道给予心宁缓释片或心宁片后,测定缺血15min(给药前)、给药后0.5h、1h、2h、3h、4h、5h、6h、8h、10h的冠脉流量,并采用HPLC法测定血浆中丹酚酸B、HJJ的浓度。结果:缓释片与普通片中丹酚酸BAUC0-∞分别为27.959mg/(mL.h)、25.970mg/(mL.h);tmax分别为4h、1h;HJJAUC0-∞分别为17.824mg/(mL.h)、15.203mg/(mL.h);tmax分别为3h、1h。其药效动力学参数比较,吸收速率常数为0.44倍、效应呈现半衰期为2.04倍、消除速率常数为0.49倍、效应消除半衰期为2.29倍、效应峰时为2.05倍。药理效应与靶器官内血药浓度之间的关系符合Hill方程。结论:建立了丹酚酸B、HJJ在犬体内PK-PD量效方程,心宁缓释片缓释特征明显。

Objective： The pharmacokinetics-pharmacodynamics methods were used to study the dese-effect relationship of Xinning Extended Action Tablet （XEAT） on dogs, meanwhile, the tablet＇s delayed release effect was also evaluated. Methods. 60 mongrel dogs were ligated on their arteria coranaria and XEAT or Xinning Tablet （XT） were given to them through their oesophagus, then, the flow rate of the arteria coranaria were measured 10 times respectively： 15 min before administered and 0.5 h,1 h,2 h,3 h,4 h,5 h,6 h,8 h,10 h after administered. Meanwhile, the concentration of Salvianolic acid-B and HJJ in plasm were determined. Results： The Salvianolic acid-B AUC0-∞, of XEAT and XT was 27. 959 mg/mL · h and 25. 970 mg/mL · h, tmax was 4h and lh respectively; HJJ AUC0-∞ was 1. 824 mg/mL · h and 15. 203mg/mL · h, tmax was 3h and lh respectively. The ratios of pharmacodynamics parameters were.0.44 times（Ka） ,2.04 times （t1/2 of effective presentation） ,0.49 times（Kel） ,2.29 times （t1/2 of effective elimination） ,2.05 times（ tmax of effectiveness）. The relationship between pharmacological effects and target organs＇ blood drug level accorded with Hill equations. Conclusion： The equations of dose-effect of PK-PD about Salvianolic acid-B and HJJ on dogs were established, which means the slow-released characteristic of XEAT is evident.