微透析法进行芎冰喷雾剂鼻腔给药的脑内药动学研究

Study on brain pharmacokinetics of Xiongbing nasal spray after intranasal administration in rats by using microdialysis method

目的:测定芎冰喷雾剂经鼻腔给药后主要成分磷酸川芎嗪(TMPP)在大鼠脑内的药代动力学参数。方法:大鼠鼻腔或静脉注射给予芎冰喷雾剂后,利用微透析技术进行脑内药动学研究,高效液相色谱法测定透析液样品中TMPP的浓度,用Das2.0药动学软件计算主要药动学参数。结果:鼻腔给药和静注给药后TMPP在脑内的吸收均符合一室模型,芎冰喷雾剂鼻腔给药与静注给药TMPP都迅速进入脑内达到峰浓度,鼻腔给药TMPP在脑内的停留时间更长。结论:微透析法能较好的反映芎冰喷雾剂鼻腔给药后TMPP的药动学特征,鼻腔给药是治疗缺血性脑血管机能不全急性期的一种速效途径。

Objective： To establish a method for detecting the brain pharmacokinetic parameters of tetramethylpyrazine phosphate（TMPP）,the main active component in Xiongbing nasal spray after intranasal administration in rats.Methods： The pharmacokinetic behavior of TMPP in rat brain was investigated after intranasal or intravenous administration of Xiongbing nasal spray,brain samples were collected by intracerebral microdialysis.The concentration of TMPP in the samples was determined by HPLC.After the dialysate concentration was calibrated,main pharmacokinetic parameters were calculated and analyzed by Das2.0.Results： The results showed that physiological disposition of TMPP was fitted to open one-compartment model after intranasal or intravenous administration.Compared with intravenous group,intranasal group has its characteristics： quick absorption,quick distribution and prolonged duration of TMPP.Conclusion： The pharmacokinetics characteristics of TMPP after intranasal administration of Xiongbing nasal spray was collected by using microdialysis method.Nasal administration is a quick-acting way for ischemic cerebral vessel insufficientia.