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

发布时间：2018-06-18 12:59

本文选题：尼索地平 + 控释贴剂　；参考：《中国药房》2015年28期

【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。
[Abstract]:Aim: to establish a pharmacokinetic-pharmacodynamic PK-PD-binding model of nisoldipine controlled-release patch (NCRP) in spontaneously hypertensive rats (SHRs). Methods: SHR were randomly divided into two groups: patch group (n = 6) and tablet group (n = 6). Microdialysis probes were implanted into each group and each group was given 5 mg of nisoldipine. Plasma microdialysate was collected within 36 hours after administration. The plasma concentration of nisoldipine was determined by high performance liquid chromatography (HPLC). The pharmacokinetic parameters were calculated by software win Nonlin 5.3. The PK-PD binding model was studied with heart rate and blood pressure as pharmacodynamic indexes. Results: compared with nisoldipine tablets, the drug effect of NCRP and the concentration of NCRP were fitted by Sigmoid-Emax model. The main parameters of PK-PD model of heart rate and systolic blood pressure were Emaxurus 2.65 卤0.06GV, EC50: 83.65 卤35.251.29 卤0.26ng / ml, 纬: 0.83 卤0.91g / ml, 纬: 0.83 卤0.351g / ml, 纬: 0.83 卤0.91kew 0.37 卤0.53h-1, respectively. The main parameters of PK-PD model of heart rate and systolic blood pressure were: Emax 2.65 卤0.87g / L EC50 卤35.251.29 卤0.26 ng / ml, 纬: 0.83 卤0.91g / ml, r: 0.83 卤0.91g / ml, r = 0.83 卤0.91g / ml, respectively. Conclusion: the PK-PD binding model of NCRP in SHR was successfully established.
【作者单位】：广东省中药研究所;广东食品药品职业学院;中山大学工学院;
【基金】：广东省医学科研基金(No.B2012063)
【分类号】：R965

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