论文部分内容阅读
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 investigate the relationship between pharmacokinetics and pharmacodynamics of CVB-D in rabbits with myocardial ischemia by means of pharmacokinetic-pharmacodynamic (PK-PD) binding model . Methods: Rabbit models of myocardial ischemia were established by ligation of coronary arteries. The concentration of CVB-D in percutaneous administration and intragastric administration was measured by microdialysis sampling technique. Lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA) activity were determined. PK-PD model was fitted with pharmacology software and the main parameters were calculated. Results: The maximal inhibitory effect of S-type was observed between the pharmacological effect and drug concentration, and the parameters of PK-PD binding model were accurately calculated. CONCLUSION: The PK-PD binding model of cyclophosphamide D in rabbits with myocardial ischemia was established. The pharmacokinetic and pharmacodynamic parameters, Cp-E curve and the pharmacodynamic parameters of each group were obtained under different routes of administration Efficacy equation.