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ρmax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tmax,AUC0-t,AUC0-∞MRT,CLs、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。
Abstract
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 ρmaxafter 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 tmaxAUC0-t,AUC0-∞,MRT and CLs 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.
关键词
盐酸川芎嗪 /
鼻腔给药 /
微透析 /
脑内药动学 /
大鼠
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Key words
tetramethylpyrazine hydrochloride(TMPH) /
intranasal administration /
microdialysis /
brain pharmacokinetics /
rat
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参考文献
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脚注
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基金
国家自然科学基金面上项目(30371781)
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