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  

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

作　　者：赖宝林[1] 王利胜[1] 夏祖猛[1] 吴阳[1] 程龙[1] 田瑶[1] 张升[1] 

机构地区：[1]广州中医药大学药剂教研室,广州510006

出　　处：《中国药学杂志》2011年第24期1906-1910,共5页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30873443)

摘　　要：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t1/2、MRT0-∞与鼻腔给药接近,但cmax、AUC0-∞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AUC0-∞与静注相比没有显著性差异,但显著延长了t1/2、MRT0-∞,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AUC0-∞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。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 mierodialysis 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 pharmacokinetic software DAS2. 1, and evaluated the brain targeting by the value of drug targeting index （DTI）. RESULTS The measured pharmacokineties of free TMP concentration in blood and brain all fited single compartment model after intragastric administration, and two-compartment model after intranansal and intravenous administration. The absolute bioavailability （F） of intragastric administration was （41.89 ± 5.16）% , t1/2 and MRT0-∞ of TMP in brain was approximate compared with intranansal administration, but the Cmax and AUC0-∞ was significantly lesser than its. The F of intranansal administration was （ 86. 60± 2. 02） %, and AUC0-∞ in brain was approximate to intravenous administration, but the t1/2 and MRT0-∞ was significantly prolonged, and increased by nearly 1.16,1.24 respectively. Its DTI value was 1.07. CONCLUSION The AUC0-∞ values of TMP in brain were approximate between intravenous and intranansal administration, part of TMP could be straight transported into brain by intranansal administration, which could improve the brain targeting of Xiongbing Microemulsion, and showed a prolonged duration of TMP concentration in the brain. Therefor,intranansal administration of Xiongbing Microemulsion could be a promising alternative to traditional administration routes.

关 键 词：芎冰微乳 川芎嗪鼻腔给药 脑靶向 微透析 

分 类 号：R944[医药卫生—药剂学]