基于微透析-UPLC技术的异嗪皮啶大鼠脑纹状体细胞外液药动学研究

Pharmacokinetics of Isofraxidin in Extracellular Fluids of Striatum in Rats Using Microdialysis-UPLC Method

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.