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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 investigate the feasibility of intranasal administration of ligustrazine (TMP) as an index component to evaluate the brain targeting of ligustrazine microemulsion via nasal administration in rats. Methods Gavage and intravenous injection were used as control. Combined with blood and brain microdialysis sampling technique, dialysate in blood and brain striatum were collected continuously from 3 routes of administration. The concentration of TMP was determined by HPLC. The recoveries After calibration, the main pharmacokinetic parameters were calculated using the DAS 2.1 pharmacokinetic software and the brain targeting index (DTI) was used as a target for brain targeting evaluation. Results The pharmacokinetics of TMP administered intragastrically in the blood and the brain all accorded with the one-compartment model. Nasal and intravenous administration conformed to the two-compartment model. The absolute bioavailability (F) of intragastric administration was (41.89 ± 5.16)%, while that of TMP in the brain was close to that of intranasal administration, but the values of cmax and AUC0-∞ were significantly lower than those of intranasal administration and DTI = 1.00; F was (86.60 ± 2.02)% in nasal administration, AUC0-∞ in brain was not significantly different from that in intravenous injection, but significantly increased t1 / 2 and MRT0-∞, increased by 1.16 and 1.24 respectively Times, DTI = 1.13. Conclusions AUC0-∞ of TMP in the brain after intranasal administration is similar to that of intravenous administration. Some drugs can be translocated directly into the brain with certain brain targeting and the drug’s residence time in the brain is longer, which is expected to become A new route of administration.