环维黄杨星D抗心肌缺血PK-PD结合模型的研究

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。

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

ABSTRACT 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 Blood samples were withdrawn at various time intervals to assess the changes in the activity of lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) in plasma. The main parameters were calculated and the PK-PD module was fitted using pharmacology software.Results: The parameters of PK-PD model were obtained 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 indicators under various conditions with different routes of administration.