磷酸川芎嗪大鼠鼻腔给药靶向脑部的药动学研究

Study on Brain Pharmacokinetics of Tetramethylpyrazine Phosphate After Intranasal Administration

目的评价磷酸川芎嗪(TMPP)经大鼠鼻腔给药后的脑部药动学特性。方法大鼠鼻腔给予或静脉注射TMPP10mg·kg-1后,利用微透析技术进行脑部药动学研究,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在脑部的吸收均符合一室模型,TMPP鼻腔给药吸收快,迅速入脑,且在脑部的停留时间更长;AUC0-∞分别为(698.26±122.59),(446.25±107.44)μg·min·mL-1,两者有显著性差异(P<0.05);Cmax分别为(8.99±2.51),(9.03±2.08)μg·mL-1;Tmax分别为(10.17±3.49),(9.86±2.94)min,均无显著性差异。结论TMPP鼻腔给药后迅速入脑,AUC0-∞值高于静脉注射,有望成为一种新的给药途径。

Objective To evaluate the rat brain pharmacokinetics of tetramethylpyrazine phosphate （TMPP） after intranasal administration. Methods The pharmacokinetic behavior of TMPP in rat brain was investigated after intranasal or intravenous administration （10mg ·kg^-1） of TMPP. Brain samples were collected by intracerebral microdialysis. The concentration of TMPP in the sample was measured by high performance liquid chromatography （HPLC）. Main pharmacokinetic parameters were calculated and analyzed by Das 2.0 pharmacokinetic software. Results The results showed that two administration methods were all fitted to one compartment model. The absorption of TMPP from the nasal cavity to brain was rapid. The concentration - time curve showed a prolonged duration of TMPP concentration in the brain after intranasal administration. AUC0- ∞ values were （698.26 ± 122.59） μg·min·mL^-1 in intranasal group and （446.25 ± 107.44） μg·min·mL^-1 in intravenous group, and the difference was significant between the two groups （ P 〈 0.05）. Cmax was （8. 99 ± 2. 51 ） μg · mL^-1 and （9.03 ± 2.08） μg· mL^-1, Tmax was （ 10. 17 ± 3.49） min and （9.86 ± 2.94） min respectively, in intranasal group and intravenous group, respectively, and the difference was insignificant. Conelusion Intranasal administration of TMPP may be a promising alternative to traditional administration routes.