盐酸川芎嗪大鼠鼻腔给药脑内药动学研究

 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ρ_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-t,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。

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

OBJECTIVE To investigate the brain pharmacokinetics of tetramethylpyrazine hydrochloride(TMPH)after intranasal administration in rats.METHODS Striatum dialysate samples were continuously collected by brain microdialysis technique in awake freely-moving rats.The concentration of TMPH in dialysate samples were measured by HPLC.The pharmacokinetic parameters were calculated by WinNonlin4.0.1 and statistically analyzed.RESULTS The TMPH concentration in striatum five minutes after in- tranasal administration was(1.43±0.29)mg·L^-1,while much lower concentration was found after intravenous injection administra- tion.The value of ρ_maxafter 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 significant difference among the values of t_maxAUC_0-t,AUC_0-∞,MRT and CL_s of the two administration routes(P>0.05).CONCLUSION TMPH could be absorbed into the brain promptly after in administration and the absorption amount was similar to iv administration.Therefore,it could be a promising alternative delivery for TMPH in the future.