目的：研究异嗪皮啶在帕金森病模型大鼠脑内的药动学特征。方法：使用鱼藤酮制作帕金森病模型大鼠，并通过行为学测试及免疫组化实验对模型进行验证。采用脑内微透析取样技术，在给予10 mg/kg和20 mg/kg异嗪皮啶后，以5、10、15、20、30、40、50、60 min为时间点进行采样，经回收率校正后，使用Winnolin 6.1 计算相应药动学参数。结果：行为学测试及免疫组化实验证明模型制作成功。在给予相关模型大鼠异嗪皮啶10 mg/kg和20 mg/kg后，相应的药动学参数分别为，t1/2=17.63±1.49 min、18.69±1.67 min，Cmax =626.38±89.69 ng/mL、1471.30±163.10 ng/mL，tmax =15 min、15 min，AUC0-t=14014.95±2927.21 ng·min/mL、35431.86±5303.36 ng·min/mL，AUC0-∞=16245.54±3446.15 ng·min/mL、41395.40±6180.62 ng·min/mL，MRT0-t=23.52±0.76 min、23.53±0.40 min，MRT0-∞=30.81±2.10min、32.68±2.39 min。结论：该方法可用于测定病理状态下口服异嗪皮啶后大鼠脑内的药动学主要参数，为临床用药提供参考。

This article was aimed to study the pharmacokinetic characteristics of isofraxidin in extracellular fluids of striatum in rat model of Parkinson's disease (PD). Rotenone was used in the establishment of PD rat model. And the model was estimated by praxiology test and immunohistochemistry experiments. Microdialysis was used to get the sample at 5, 10, 15, 20, 30, 40, 50 and 60 min after the single oral administration of isofraxidin at the amount of 10 mg/kg and 20 mg/kg respectively. The results were revised by relative recovery in vivo, and the pharmacokinetic parameters were calculated through non-compartment model method with WinNonlin 6.1 program. The results showed that the established model was proved to be a success by the praxiology test and immunohistochemistry experiments. The main pharmacokinetic parameters of isofraxidin in extracellular fluids of striatum in rats after a single oral administration of isofraxidin at the amount of 10 mg/kg and 20 mg/kg were t1/2=17.63±1.49 min and 18.69 ±1.67 min; Cmax = 626.38 ±89.69 ng/mL and 1471.30 ±163.10 ng/mL; tmax = 15 min and 15 min; AUC0-t = 14014.95±2927.21 ng?min/mL and 35431.86±5303.36 ng?min/mL; AUC0-∞= 16245.54±3446.15 ng?min/mL and 41395.40±6180.62 ng?min/mL; MRT0-t = 23.52±0.76 min and 23.53±0.40 min;MRT0-∞= 30.81±2.10 min and 32.68±2.39 min. It was concluded that this method can determine the main pharmacokinetic parameters of isofraxidin in extracellular fluids of striatum in pathological rats after a single oral administration of isofraxidin. And it can provide a certain reference for the clinical practice.

国家自然科学基金青年科学项目（30901974）：刺五加治疗帕金森病有效成分的药动学及药物代谢轮廓研究，负责人：卢芳；教育部“春晖计划”合作科研项目（Y-30）：基于微透析-UPLC 技术的刺五加治疗PD 有效组分脑内药动学研究，负责人：卢芳；科学技术部国家“重大新药创制”科技重大专项项目（2009ZX09103）：刺五加有效组分优化体治疗帕金森病的成药性研究，负责人：刘树民；黑龙江中医药大学优秀创新人才支持计划资助，负责人：卢芳。