目的：考察大鼠口服给药异嗪皮啶（Isofraxidin）之后的脑纹状体细胞外液药动学特性。方法：大鼠单次灌胃给予异嗪皮啶10 mg·kg-1和20 mg·kg-1后，采用脑微透析活体取样技术和超高效液相色谱质谱联用技术（UPLC-MS），测定给药后60 min内各时间点大鼠脑纹状体细胞外液中透析液异嗪皮啶的浓度，经回收率校正后，采用WINONLIN 6.1程序以非房室模型法拟合药动学参数。结果：大鼠单次灌胃给予异嗪皮啶10 mg·kg-1和20 mg·kg-1后，其主要药动学参数分别为AUC0-∞（13973.88±1582.984）、（28059.76±4207.66）ng·min·mL-1；t1/2（16.68±0.49）、（17.41±2.88）min；Cmax（498.87±64.36）、（899.81±133.22） ng·mL-1；tmax均为15 min，其中Cmax和tmax均为实测值。结论：异嗪皮啶经大鼠口服给药后能够迅速透过血脑屏障，到达纹状体部位，15 min浓度达到最大值，之后药物以较快速率消除，纹状体细胞外液异嗪皮啶浓度具有明显的剂量依赖性。

This study was aimed to observe the pharmacokinetic characteristics of isofraxidin in extracellular fluids of striatum in rats after oral administration of isofraxidin. Microdialysis and UPLC-MS analytical technology were employed in the study to detect the concentration of isofraxidin in microdialysis dialysate of extracellular fluids of striatum in rats, within 60 min after a single oral administration, with isofraxidin of 10 mg·kg-1 and 20 mg·kg-1, respectively. The results were revised by relative recovery in vivo. The pharmacokinetic parameters were calculated through non-compartment model method with software of WINONLIN 6.1 program. Main pharmacokinetic parameters of isofraxidin in extracellular fluids of striatum in rats after a single oral administration of isofraxidin at 10 mg·kg-1 and 20 mg·kg-1 were AUC0-∞(13973.88±1582.984) and (28059.76±4207.66) ng·min·mL-1; t1/2(16.68±0.49) and (17.41±2.88) min; Cmax(498.87±64.36) and (899.81±133.22) ng·mL-1. The tmax of both two groups was 15 min. Both the Cmax and tmax were measured. It is concluded that isofraxidin quickly permeates the blood-brain barrier and reaches the striatum. The maximal concentration of isofraxidin is 15 min after oral administration. And then the concentration decreases at a faster rate. It shows a significant dose-dependent phenomenon of the concentration of isofraxidin in extracellular fluids of striatum in rats.

国家自然科学基金青年科学基金项目（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；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；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。