冰片作用下尼莫司汀(ACNU)透过血脑屏障的药动学研究.doc

冰片作用下尼莫司汀（ACNU）透过血脑屏障的药动学研究 史卫忠1，赵志刚2 （1. 北京大学医学部药学院临床药学系，北京市 100083； 2. 首都医科大学附属北京天坛医院药剂科，北京市 100050） 摘要：目的：研究冰片作用下尼莫司汀（ACNU）透过血脑屏障的药动学改变。方法：，将日本大耳白兔随机对照分为冰片组和对照组，采集不同时间点的血液和脑脊液，HPLC 法测定尼莫司汀的浓度，药物浓度－时间曲线经3P97 程序拟合，比较主要药动学参数。结果：合用冰片后脑脊液中尼莫司汀的 Tmax、Cmax 和 AUC 均增加，血脑屏障通透率提高18.66%。证明冰片可提高尼莫司汀的生物利用度，增加其在脑脊液的分布,有效促进尼莫司汀通过血脑屏障。 关键词：尼莫司汀,冰片,血脑屏障,高效液相色谱法,药代动力学 Pharmacokinetical Study of Nimustine (ACNU) through Blood Brain Barrier after Intragastric Administration of Borneol Shi wei-zhong1,Zhao zhi-gang2(1. Clinical Pharmacy College,Peking University Health Science Center, Beijing 100083, China;2. Department of pharmacy, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China) ABSTRACT: Objective: To observe the effect of borneol on the pharmacokinetics of Nimustine through Blood Brain Barrier in rabbits.Method: Japanese White Rabbits were randomly divided into control group and borneol group.Blood and CSF samples were obtained after intravenous injection of nimustine with/without Borneol in different times.The concentrations of TMZ in plasma and cerebrospinal fluid were determined by high performance liquid chromatography . The plasma/CSF concentration-time curves were fitted and the pharmacokinetic parameters were calculated with 3P97 practical pharmacokinetic program and compare the change of pharmacokinetics of nimustine after intragastric administration of borneol. Result: Tmax、Cmax and AUC were increased in borneol group and the permeability of Blood Brain Barrier(BBB) was increased by 18.66%. Borneol can increase the bioavailability of ACNU in CSF.The increase of concentration of nimustine in the CSF of rabbits suggests that borneol can improve the permeability of BBB. [基金项目]北京市优秀人才培养专项经费个人资助项目((编号:20061D0300415). 作者简介：史卫忠, 男, 硕士研究生 通讯作者：赵志刚, 男, 主任药师, Tel: 010 E-mail:1022zzg@ Keywords：Nimustine(ACNU),Borneol, Blood Brain Barrier, High Performance Liquid Chromatogram, Pharmacokinetics 尼莫司汀（Nimustine Hydrochloride，ACNU）是一种亚