冰片作用下替莫唑胺在家兔体内的药代动力学研究.doc

冰片作用下替莫唑胺在家兔体内的药代动力学研究 李红霞，黄佳，史卫忠，赵志刚*（首都医科大学附属北京天坛医院药剂科， 北京100050） 摘要：目的家兔血浆和脑脊液中替莫唑胺的高效液相色谱法HPLC)检测方法，比较冰片作用后药动学的改变。方法 健康日本大耳白兔（2.5 ± 0.5kg），随机分为组和对照组。组以冰片0.7g·kg的剂量灌胃1h后，替莫唑胺12mg·kg灌胃；对照组灌服等量75％乙醇后，相同剂量灌胃替莫唑胺。采集不同时间点的血液和脑脊液， HPLC测定替莫唑胺的浓度，药物浓度－时间经3P97程序拟合，进行自动模型判别和参数计算。结果 替莫唑胺在0.1～20μg·ML1范围内线性关系良好，其血液回归方程为p＝0.0723c＋6×10-6r＝0.9998；脑脊液回归方程为p＝0.0734c＋0.0054r＝0.9997；平均回收率在75％以上。R969.1 文献标识码The Pharmacokinetics of Temozolomide in Rabbits after Intragastric Administration of Borneol LI Hong-xia, HUANG Jia, Shi Wei-zhong, ZHAO Zhi-gang *（Department of pharmacy, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing 100050, China) Abstract: OBJECTIVE: To develop the high-performance liquid chromatographic analysis of temozolomide (TMZ) in rabbit plasma and cerebrospinal fluid (CSF); To compare the change of pharmacokinetics of TMZ after intragastric administration of Borneol. METHODS: White [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：李红霞, 女, 硕士研究生 通讯作者：赵志刚, 男, 主任药师, Tel: 010 E-mail:1022zzg@ Rabbits（2.5 ± 0.5 kg）The concentrations of TMZ in plasma and cerebrospinal fluid were determined by HPLC which involved selection of metronidazole as internal standard (I.S) followed by separation on a reversed phase C-18 column and quantification by UV absorbance at 329 nm. Blood and CSF samples were obtained after intragastric administration of TMZ 12 mg·kg-1 with/without Borneol 0.7g·kg-1 at different time.The plasma/CSF concentration-time curves were fitted and the pharmacokinetic parameters were calculated with 3P97 practical pharmacokinetic program. Results: The standard curve of TMZ was linear over the range 0.1-20μg·ml-1. Its regression equation was p＝0.0723c＋6×10-6r＝0.9998p＝0.0734c＋0.0054r＝0.9997. The average recovery of temozolomide was more than 75%.The pharmacokinetics of temozolomide in rabbit could be respectively described by a two compartment model in plasma and a one compartment model in CSF. Tpeak, Cmax and AUC were increased i