中国药理学通报2017，Vol.33Issue(4)：552-556,5.DOI:10.3969/j.issn.1001-1978.2017.04.020
黄连碱对内毒素发热大鼠解热作用的PK-PD研究
Pharmacokinetic-pharmacodynamic study on antipyreticeffects of coptisine on endotoxin-induced pyrexia of rats
摘要
Abstract
Aim To establish the pharmacokinetic-pharmacodynamic(PK-PD) modeling to characterize the antipyretic effects of coptisine, an active component in coptis chinensis on rats.Methods Nine healthy male Sprague-Dawley(SD) rats were randomly divided into three groups, each with three.The rats in the first group were injected intravenously with lipopolysaccharide(LPS,100 μg·kg-1) alone.The second and third group rats were given coptisine high-dose(3.87 mg·kg-1) and coptisine low-dose(1.93 mg·kg-1) by tail vein injection at 30 min after LPS injection, respectively.Body temperature was measured at different time points, and blood samples from tail vein were collected simultaneously.The blood concentration of coptisine was determined by ultra performance liquid chromatography.Monolix software was used to model PK-PD of coptisine mean plasma concentration and temperature effects,by population computation with non-covariates.Besides.the model with advantage was selected by the fitting goodness.Results Coptisine could inhibit body temperature of endotoxin-induced fever in rats significantly.Two-compartment linear elimination model was used to describe the final PK model.Gaussian function, an input function of body temperature changes, which was used to depict PD model, the PK and PD models were connected by the Emax model.At last, the final model was fitted better;the fitting results indicated that the EC50 of antipyretic effect of coptisine was 89.7 μg·L-1, and the Emax was 1.88℃.Conclusions Coptisine has a powerful anti-pyretic effect on endotoxin-induced pyrexia of rats with high potency, Low in vivo distribution and quick clearance.关键词
黄连碱/内毒素/解热/药动学-药效学/静脉注射/体温Key words
coptisine/endotoxin/antipyretic/pharmacokinetic-pharmacodynamic/intravenous injection/body temperature分类
医药卫生引用本文复制引用
王丽,胡樱凡,童东,左芳,魏志成,孟宪丽,王平..黄连碱对内毒素发热大鼠解热作用的PK-PD研究[J].中国药理学通报,2017,33(4):552-556,5.基金项目
国家自然科学基金资助项目(No 81274111) （No 81274111）
