异丙酚前药HX0891和HX0892在大鼠体内的初步药效学评价  

Initial pharmacodynamics evaluation of Propofol prodrug HX0891 and HX0892 in the rats

作　　者：周毅[1] 杨俊[2] 康仪[2] 张文胜[2] 

机构地区：[1]四川大学华西药学院,四川成都610041 [2]四川大学华西医院麻醉与危重急救研究室,四川成都610041

出　　处：《华西药学杂志》2012年第1期45-47,共3页West China Journal of Pharmaceutical Sciences

摘　　要：目的通过体内和体外实验对异丙酚前药HX0891和HX0892进行初步药效学评价。方法稳定性实验证明体内实验中给予的前药没有分解;体外血浆释放实验证明两个前药是否能分解产生异丙酚;体内实验用上下法测定两个前药的半数有效量(ED50),并和异丙酚和磷丙泊酚钠进行药效学对比。结果 HX0892的体外血浆分解量大于HX0891,分解速度也快于HX0891;体内实验中,HX0891、HX0892的ED50分别为121.76、98.40 mg.kg-1,在等效剂量下,二者的维持时间都比异丙酚和磷丙泊酚钠显著加长。结论 HX0891和HX0892的起效时间慢,但维持时间显著延长,可能适用于临床镇静;二者的安全性与有效性需进一步研究。OBJECTIVE To evaluation initial pharmacodynamic of HX0891 and HX0892 was conducted in rats by in vitro and in vivo studies.METHODS Stability study was conducted to guarantee that no propofol was released before injection.HX0891 and HX0892 were added into the plasma of rat respectively to observe the release of propofol.ED50 of HX0891 and HX0892 in rats was determined by up-and-down method.Pharmacodynamic comparsion with propofol and fospropofol was also conducted.RESULTS Conversion rate and degree of HX0892 was greater than that of HX0891.ED50 of HX0891 and HX0892 were 121.76 mg·kg-1 and 98.40 mg·kg-1,respectively.The duration time of these two compounds in blood was significantly longer than that of propofol and fospropofol.CONCLUSION The onset time of HX0891 and HX0892 was delayed with a longer duration time.Maybe they can be used for sedation.More studies were needed to investigate the efficacy and safety of these two compounds.

关 键 词：异丙酚 水溶性 前药 药效学 

分 类 号：R96[医药卫生—药理学]