黄芩苷对角叉菜胶致热大鼠解热作用的PK-PD模型研究  

Pharmacokinetic-pharmacodynamic study on antipyretic effects of baicalin on carrageenan-induced pyrexia of rats

作　　者：于宜平[1] 张艳[1] 李红[1] 王平[1] 孟宪丽[1] 陈小睿[1] 曾勇[1] 

机构地区：[1]成都中医药大学药学院,四川成都611137

出　　处：《中草药》2014年第4期527-531,共5页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81073118);教育部高校博士点基金项目(20105132120003);四川省教育厅自然基金重点项目(11ZA061)

摘　　要：目的利用药动学-药效学(PK-PD)结合模型评价黄芩苷解热作用的强度和特点。方法采用角叉菜胶复制大鼠炎症发热模型,ig黄芩苷(180 mg/kg)后不同时间点采血、测量体温;高效液相色谱-质谱(HPLC-MS)法测定黄芩苷血药浓度;以ADAPT软件拟合基于作用机制的各PK-PD模型,以拟合优度选取优势模型。结果最终确定了含肝肠循环的双部位吸收PK模型和Sigmoid Imax PD模型,并以效应室抑制产热的方式联结了PK和PD模型。拟合结果表明,黄芩苷解热作用的Imax为0.56℃,PD形状参数(H)为10.67。结论黄芩苷对抗角叉菜胶致发热作用的量效关系范围窄,效能低。Objective Pharmacokinetic-pharmacodynamic （PK-PD） modeling is used to charac＇terize the antipyretic effects ofbaicalin （BA） in rats. Methods Twelve healthy male Sprague-Dawley （SD） rats were randomly divided into two groups, each with six. The rats in the first group were sc injected with carrageenan （1 mL per rat） alone to make the inflammation model. The rats in the second group were given BA （180 mg/kg） by ig administration after carrageenan injection. Body temperature was measured while orbital sinus blood sample was collected at different time points. The blood concentration of^BA was determined by high performance liquid chromatography-mass spectrometry. PK-PD modelings were fitted with ADAPT 5.1 software. The model with advantage was selected by the fitting goodness. Results The concentration-time curve was best and fitted by double-site absorption with enterohepatic circulaion of Pk model and the antipyretic responses of Sigmoid-Imax PD model could be well confirmed. The PK and PD models were reconnected by the antipyretogenetic inhibition with effect compartment. The fitting results indicated that the Imax of antipyretic effect by BA was 0.56 ℃ and shape parameter （H） for PD was 10.67. Conclusion The dose-effect relationship range in the antipyretic activity of BA on carrageenan-induced pyrexia of rats is narrow and its efficiency is low.

关 键 词：黄芩苷 药动学-药效学模型 发热 体温 角叉菜胶 

分 类 号：R285.5[医药卫生—中药学]