微透析采样技术进行芎冰微乳经大鼠鼻腔给药的脑靶向性研究

 目的 以川芎嗪（TMP）为指标成分，评价芎冰微乳经大鼠鼻腔给药的脑靶向性，探讨鼻腔给药的可行性。方法 以灌胃、静脉注射给药为对照，结合血液和脑部微透析采样技术，连续收集3种给药途径大鼠血液、脑纹状体中的透析液，HPLC测定TMP浓度，经回收率校正后，用DAS2.1药动学软件计算主要药动学参数，以脑靶向指数(DTI)为指标进行脑靶向性评价。结果 灌胃给药TMP在血液、脑内的药动学过程均符合一室模型，鼻腔、静注给药均符合二室模型。灌胃给药绝对生物利用度(F)为（41.89±5.16）%，TMP在脑内的t_1/2、MRT_0-∞与鼻腔给药接近，但c_max、AUC_0-∞显著小于鼻腔给药，DTI=1.00；鼻腔给药的F为（86.60±2.02）%，脑内的AUC_0-∞与静注相比没有显著性差异，但显著延长了t_1/2、MRT_0-∞，分别增加了1.16、1.24倍，DTI=1.13。结论 鼻腔给药后TMP在脑内的AUC_0-∞与静注给药相似，部分药物可直接转运入脑，具有一定的脑靶向性，且药物在脑部的驻留时间更长，有望成为一种新的给药途径。

Evaluation of Brain Targeting in Rats of Xiongbing Microemulsion Nasal Delivery by the Microdialysis Technique

OBJECTIVE To evaluate the brain targeting of intranansal administration Xiongbing microemulsion and investigate its feasibility by the representative constituent of tetramethylpyrazine(TMP).METHODS Blood and striatum dialysate samples were continuously collected by blood and brain microdialysis technique in rats after intragastric(ig),intravenous(iv) and intranansal(in) administration.The concentration of TMP in dialysate samples were measured by HPLC,the pharmacokinetic parameters were calculated by pharma...