Comparative pharmacokinetics of tetramethylpyrazine phosphate in rat plasma and extracellular fluid of brain after intranasal,intragastric and intravenous administration

作     者：Dongmei Meng Haoyang Lu Shanshan Huang Minyan Wei Pingtian Ding Xianglin Xiao Yuehong Xu Chuanbin Wu 

作者机构：School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China The First Affiliated Hospital of Guangzhou Medical CollegeGuangzhou 510120China School of PharmacyShenyang Pharmaceutical UniversityShenyang110016China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2014年第4卷第1期

页      面：74-78页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 10[医学] 

基　　金：The authors gratefully acknowledge the financial support by Department of Science and Technology Guangdong China(2010B03070009). 

主　　题：Tetramethylpyrazine phosphate Intranasal delivery Pharmacokinetics Microdialysis Rat 

摘      要：The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate(TMPP)in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes:intranasal(i.n.),intragastric(i.g.)and intravenous(i.v.)administration.After i.n.,i.***.and i.***.administration of a single-dose at 10 mg/kg,cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals.The concentration of TMPP in the samples was analyzed by HPLC.The area under the concentration-time curve(AUC)and the ratio of the AUCbrain to the AUCplasma(drug targeting efficiency,DTE)was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration.After i.***.administration,TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex(t_(max)=15 min).The ratio of the AUCbrain dialysates value between i.***.route and i.***.injection was 0.68,which was greater than that obtained after i.***.administration(0.43).The systemic bioavailability obtained with i.***.administration was greater than that obtained by the i.***.route(86.33%vs.50.39%),whereas the DTE of the nasal route was 78.89%,close to that of oral administration(85.69%).These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation,and then crosses the blood-brain barrier(BBB)to reach the cerebral cortex.Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches.