盐酸川芎嗪大鼠鼻腔给药脑内药动学研究  

Studies on Brain Pharmacokinetics of Tetramethylpyrazine Hydrochloride after Intranasal Administration in Rats

作　　者：李范珠[1] 冯耀荣[1] 冯健[1] 

机构地区：[1]浙江中医药大学药学院,杭州310053

出　　处：《中国药学杂志》2008年第6期452-454,共3页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金面上项目(30371781)

摘　　要：目的研究盐酸川芎嗪(TMPH)经大鼠鼻腔给药后的脑内药动学特性。方法采用脑微透析取样技术,以清醒自由活动大鼠为实验模型,连续收集盐酸川芎嗪鼻腔和静脉注射给药后大鼠脑内纹状体透析液,HPLC测定其浓度,并经回收率校正后,以WinNonlin4.0.1药动学软件处理,计算药动学参数并进行统计学分析。结果TMPH鼻腔给药5 min后脑纹状体中的药物浓度为(1.43±0.29)mg·L^(-1),而静脉注射后在相同时间点入脑不显著。鼻腔给药的p_(max)低于静脉注射,分别为(3.43±0.46)和(4.67±0.76)mg·L^(-1),但二者的t_(max),AUC_(0-1),AUC_(0-∞)MRT,CL_s、近似,无显著性差异(P>0.05)结论TMPH鼻腔给药后可迅速吸收入脑,且吸收量与静脉注射近似,因此有望成为一种新的给药途径。OBJECTIVE To investigate the brain pharmacokinetics of tetramethylpyrazine hydrochloride（TMPH）after intranasal administration in rats. METHODS Striatum dialysate samples were continuously collected by brain mierodialysis technique in awake freely-moving rats. The concentration of TMPlt in dialysate samples were measured by HPLC. The pharmaeokinetie parameters were calculated by WinNonlin4. 0. 1 and statistically analyzed. RESULTS The TMPH concentration in striatum five minutes after intranasal administration was （ 1.43 ± 0. 29） mg·L^-1, while much lower concentration was found atier intravenous injection administration. The value of p after intranasal administration was （3.43 ± 0. 46） mg · L^-1, lower than the value of intravenous injection, （4.67 ±0. 76） mg ·L^-1. However, there was no signitieant rill＇terence among the values of tmax AUC0-∞, AUC0-∞ , MRT and CLs of the two administration routes（ P 〉0.05 ）. CONCLUSION TMPH coohl be absorbed into the brain promptly after in administration and the ahsorption amount was similar to iv administration. Therefore, it could be a promising alternative delivery tot TMPH in the future.

关 键 词：盐酸川芎嗪 鼻腔给药 微透析 脑内药动学 大鼠 

分 类 号：R969.1[医药卫生—药理学]