尼索地平控释贴剂在自发性高血压大鼠体内的药动学-药效学结合模型的建立  

Study on the Pharmacokinetic-pharmacodynamic Model of Nisoldipine Controlled-release Patches in Spontaneously Hypertensive Rats

作　　者：聂阳[1,2] 许良葵[2] 李博[2] 朱俊访[2] 陈新颖[3] 

机构地区：[1]广东省中药研究所,广州510520 [2]广东食品药品职业学院,广州510520 [3]中山大学工学院,广州510006

出　　处：《中国药房》2015年第28期3915-3917,共3页China Pharmacy

基　　金：广东省医学科研基金(No.B2012063)

摘　　要：目的:建立尼索地平控释贴剂(NCRP)在自发性高血压大鼠(SHR)体内的药动学-药效学(PK-PD)结合模型。方法:将SHR随机分为贴剂(NCRP)组和片剂(尼索地平片)组,每组6只,植入微透析探针,按尼索地平计每只给药5 mg。收集给药后36 h内的血浆微透析液,采用高效液相色谱法测定尼索地平血药浓度,Win Nonlin 5.3软件计算药动学参数,以心率和血压为药效学指标,进行PK-PD结合模型研究。结果:与尼索地平片比较,NCRP具有控释效果;NCRP药物效应与效应室浓度以Sigmoid-Emax模型拟合,心率和收缩压的PK-PD模型主要参数分别为Emax:(2.65±0.06)、(10.71±0.87),EC50:(83.65±35.25)、(1.29±0.26)ng/ml,γ:(0.83±0.91)、(1.2±0.35),Keo:(0.37±0.53)、(0.91±0.24)h-1。结论:成功建立了NCRP在SHR体内的PK-PD结合模型。OBJECTIVE：To establish the pharmacokinetic-pharmacodynamic（PK-PD） model of Nisoldipine controlled-release patches（NCRP）in spontaneously hypertensive rats（SHR）. METHODS：SHR were randomized into a patch（NCRP）group and a tablet（Nisoldipine tablets）group,with 6 rats in each group. The microdialysis probes were implanted in SHR. Each rat was given 5 mg nisoldipine. Plasma microdialysate was collected within 36 h after administration. HPLC was adopted to determine the plasma concentration of nisoldipine,and WinNonlin 5.3 was employed to calculate Pharmacokinetic parameters. With heart rate and blood pressure as pharmacodynamic indexes,PK-PD model study was conducted. RESULTS：Vs. nisoldipine tablets,NCRP has con-trolled release effect. The relationship between NCRP drug effect and effect-site concentration met the Sigmoid-Emax model. The main parameters of the PK-PD model for heart rate and systolic blood pressure were as follows as Emax of （2.65 ± 0.06） and （10.71 ± 0.87）,EC50 of （83.65 ± 35.25） and （1.29 ± 0.26） ng/ml,γ of （0.83 ± 0.91） and （1.2 ± 0.35）,Keo of （0.37 ± 0.53） and （0.91±0.24）h-1. CONCLUSIONS：PK-PD model of NCRP in SHR has been established successfully.

关 键 词：尼索地平 控释贴剂 微透析 自发性高血压大鼠 药动学-药效学结合模型 

分 类 号：R285[医药卫生—中药学]