环维黄杨星D抗心肌缺血PK-PD结合模型的研究  

Study on Pharmacokinetic-pharmacodynamic Characteristics of Cyclovirobuxine D in Myocardial Ischemia Rabbit Model

作　　者：张鹰[1] 刘新国[1] 马浩然[1] 张红[1] 

机构地区：[1]武汉市第一医院,武汉430022

出　　处：《中国药师》2015年第9期1469-1474,共6页China Pharmacist

基　　金：武汉市卫生局临床医学科研项目(编号:WZ14Z07)

摘　　要：目的:应用药动学-药效学(PK-PD)结合模型的研究方法考察环维黄杨星D(CVB-D)在心肌缺血家兔体内的药动学和药效学之间的关系。方法:以冠状动脉结扎方法制备家兔心肌缺血模型,运用微透析采样技术考察CVB-D经皮给药和灌胃给药后在心肌组织内的浓度变化,分时采血检测试验动物血浆中乳酸脱氢酶(LDH)、肌酸激酶(CK)、丙二醛(MDA)活性变化,用药物学软件拟合PK-PD模型,并计算主要参数。结果:药理效应与药物浓度之间符合抑制性S型最大效应模型,并准确计算出PK-PD结合模型参数。结论:建立了环维黄杨星D在心肌缺血家兔体内的PK-PD结合模型,得到药动学和药效学参数,Cp-E曲线以及各个药效指标在不同给药途径条件下的量效方程。Objective： To explore the relationship of pharmacokinetics （PK） and pharmacodynamics （PD） by the combined PK- PD module for cyclovirobuxine D used in myocardial ischemia in rabbits. Methods： In the study, myocardial ischemia was induced by coronary artery ligation. Microdialysis was then applied as a sampling technique to ascertain the changes in the drug concentration in myocardial tissue after percutaneous and oral administration. Blood samples were withdrawn at various time intervals to assess the chan- ges in the activity of lactate dehydrogenase （LDH）, creatine kinase （CK） and malondialdehyde （MDA） in plasma. The main parame- ters were calculated and the PK-PD module was fitted using pharmacology software. Results： The parameters of PK-PD model were ob- tained and the relationship between the pharmacologic effect and the drug concentration met the requirements of the inhibitory sigmoid- maximum effect model. Conclusion： A.PK-PD model of cyclovirobuxine D used in the treatment of myocardial ischemia in rabbits and the PK-PD parameters are obtained. Dose-effect equations are successfully established for Cp-E graphs and various pharmacological in- dicators under various conditions with different mutes of administration.

关 键 词：环维黄杨星D 心肌缺血 微透析 药动学-药效学结合模型 

分 类 号：R969.1[医药卫生—药理学]