灯盏花素不同给药途径脑内药物分布的比较

本文比较了灯盏花素鼻腔给药、口服给药与静脉给药在大鼠脑内的药物分布。采用SD大鼠尾静脉注 射、经鼻给药和灌胃0.4 mg·kg^-1灯盏花素后, 于一定时间点用小脑延髓池穿刺术采集大鼠脑脊液, ¹²⁵I标记法测定其在大鼠脑脊液，以及大脑、小脑、延脑、嗅区和嗅球等脑组织及血浆中药物含量, 梯形法分别计算其AUC。结果显示鼻腔给药组大鼠脑脊液、大脑、小脑、延脑、嗅区、嗅球及血浆中AUC_{0-240 min} (μg·min·g^-1) 分别为11.686 ± 1.919, 5.676 ± 1.025, 7.989 ± 0.925, 7.956 ± 1.159, 17.465 ± 2.136, 24.2 ± 2.906和78.51 ± 12.05; 静脉给药组AUC_{0-240 min}分别为6.79 ± 0.661, 6.251 ± 0.40, 10.805 ± 1.161, 9.146 ± 1.04, 9.892 ± 1.532, 7.871 ± 0.842和173.91 ± 10.02; 口服给药组AUC_{0-240 min}分别为0.868 ± 0.167, 1.708 ± 0.266, 2.867 ± 0.725, 2.067 ± 0.313, 1.361 ± 0.308, 1.206 ± 0.255和 45.2 ± 7.52。口服、静脉注射、鼻腔给药后脑组织的AUC_{0-240 min}分别为血浆AUC_{0-240 min}的22.29%, 29.18%, 95.49%, 说明鼻腔给药的吸收率高于口服给药和静脉给药, 并且鼻腔给药后药物在脑组织中分布较高, 其与药效的关系值得进一步探讨。

Comparison of the distribution of breviscapine in the brain by different administration routes

By comparing the drug distribution of breviscapine administered intranasally, orally and intrgvenous injected in rats’ brain.  After 0.4 mg·kg^-1 breviscapine was given by tail vein, intranasal and gastric perfusion administration to SD rats, cerebrospinal fluid was obtained by erebellomedllery cisternal puncture at different times. ¹²⁵I labeling was used to determine the drug content of cerebrospinal fluid, cerebrum, cerebellum, medulla oblongata, olfactory region, olfactory bulb and blood in rats.  AUCs were calculated by trapezoidal rule.  The results showed that AUCs_{0-240 min} (μg·min·g^-1) of brain tissues were 11.686 ± 1.919, 5.676 ± 1.025, 7.989 ± 0.925, 7.956 ± 1.159, 17.465 ± 2.136, 24.2 ± 2.906 and 78.51 ± 12.05, respectively, in the intranasal administration group; while those in the tail vein administration groups were 6.79 ± 0.661, 6.251 ± 0.40, 10.805 ± 1.161, 9.146 ± 1.04, 9.892 ± 1.532, 7.871 ± 0.842 and 173.91 ± 10.02; and oral administration group were 0.868 ± 0.167,  1.708 ± 0.266, 2.867 ± 0.725, 2.067 ± 0.313, 1.361 ± 0.308, 1.206 ± 0.255 and 45.2 ± 7.52, respectively.  AUCs_{0-240 min} of the brain tissues after oral, tail vein and intranasal administration were 22.29%, 29.18%, 95.49% of that of blood, respectively, it means that the absorption rate and drug distribution in the brain tissues after intranasal administration were higher than those of oral and tail vein administration.  It is worth to investigate further the pharmacodynamic relationship.