微透析技术对芎冰微乳在清醒大鼠脑局部的药动学研究  

Studies on Brain Pharmacokinetics of Xiongbing Microemulsion by Microdialysis Technique in Awake and Freely-moving Rats

作　　者：王利胜[1] 赖宝林[1] 夏祖猛[1] 张升[1] 吴阳[1] 程龙[1] 田瑶[1] 

机构地区：[1]广州中医药大学中药学院,广州510006

出　　处：《中药新药与临床药理》2011年第3期299-303,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金资助项目(30873443)

摘　　要：目的评价芎冰微乳灌胃、静脉注射和鼻腔给药三种不同给药途径川芎嗪(TMP)在脑部的药动学特性。方法采用脑微透析取样技术,以清醒大鼠为实验模型,连续收集三种给药途径大鼠脑纹状体透析液,HPLC法测定TMP浓度,经回收率校正后,用DAS2.1药动学软件计算主要药动学参数。结果灌胃、静注和鼻腔给药TMP在脑内药动学过程均符合一室模型,MRT0-∞分别为73.7,38.8,70.6 min;Tmax分别为15,5,15 min;Cmax分别为249.2,2579.3,1175.1μg.L-1,AUC0-∞分别为19806.9,106410.7,62973.3μg.min.L-1,TMP在脑组织中的局部生物利用度显示,鼻腔给药为59.2%,灌胃给药为18.6%。结论芎冰微乳灌胃给药生物利用度较低;静脉注射TMP入脑迅速,生物利用度最高,但代谢迅速,作用时间短;鼻腔给药生物利用度较高,且脑内作用时间较长,具有一定的研究价值。Objective To investigate the brain pharmacokinetics of tetramethylpyrazine（TMP） in Xiongbing Microemulsion after intragastric（i.g.）,intravenous（i.v.） and intranasal（i.n.） administration.Methods Striatum dialysate samples were continuously collected by brain microdialysis technique in awake and freely-moving rats after the three routs of administration.The concentration of TMP in dialysate samples were measured by HPLC.The pharmacokinetic parameters were calculated by pharmacokinetic software DAS2.1.Results All of the measured pharmacokinetics of free cerebral TMP concentration fitted single-compartment model after i.g.,i.v.and i.n.administration.The MRT0-∞,was 73.7,38.8,70.6 min,Tmax was 15,5,15 min,Cmax was 249.2,2579.3,1175.1 μg·L-1,and AUC0-∞ was 19806.9,106410.7,62973.3 μg·min·L-1,respectively.The local bioavailability of TMP in the brain was 59.2 % after i.n.administration,and 18.6 % after i.g.administration.Conclusion The bioavailability of Xiongbing Microemulsion is quite low after i.g.administration.On the contrary,Xiongbing microemulsion has the greatest bioavailability after i.v.administration,and TMP can be absorbed into the brain rapidly and then goes into rapid metabolism,which results in the short residence time in the brain.Xiongbing microemulsion has higher bioavailability after i.n administration,and the mean residence time in the brain is longer,which shows certain value for further research of Xiongbing Microemulsion by i.v.administration.

关 键 词：芎冰微乳 川芎嗪 给药途径 微透析 药动学 

分 类 号：R285.5[医药卫生—中药学]