紫杉醇脂质体在家兔体内的药动学研究  

Study on Pharmacokinetics of Paclitaxel-liposome in Rabbit

作　　者：刘韬[1] 黄红兵[1] 林子超[1] 刘庆[1] 林伊拉[2] 邓丽婷[3] 廖海[3] 

机构地区：[1]华南肿瘤学国家重点实验室中山大学附属肿瘤医院药剂科,广东广州510060 [2]广东化工制药职业技术学院,广东广州510520 [3]中山大学肿瘤医院内科,广东广州510060

出　　处：《现代食品与药品杂志》2007年第5期5-7,共3页JOurnal of Modern Food and Pharmaceuticals

基　　金：广东省科技计划项目(No:2005B30101004)

摘　　要：目的 建立家兔血浆中紫杉醇HPLC检测方法，研究紫杉醇脂质体在家兔体内的药动学规律。方法家兔血样采用叔丁基甲醚提取后在Hypersil C18柱上以甲醇：水（65：35）为流动相，检测波长为227nm，地西泮为内标条件下进行检测。结果血药浓度在0．1—40．0mg／L范围内线性关系良好（r=0．9997），提取回收率大于82．0％，日内、日间精密度分析RSD〈6．0％。用本法对家兔耳缘静脉注射紫杉醇脂质体（12mg／kg）后药动学进行研究，经DAS2．0软件拟合，脂质体制剂中紫杉醇血药浓度经时曲线符合二室模型，主要药动学参数如下：t1／2d为1．21±0．21h，t1／2p为33．56±6．69h，Vd为0．81±0．09L，CL为0．04±0．01L／h，AUC0-t为321．11±18．46mg·h^-1·L^-1，AUC0→∞为722．20±170．36mg·h^-1·L^-1，K10为0．04±0．01／h，K12为0．25±0．04／h，K21为0．32±0．06／h。结论 本实验方法简便易行，结果可靠，可用于紫杉醇脂质体的药动学研究。Objective A HPLC method was developed for the determination of paclitaxel in rabbit blood, and to study the pharmacokinetic parameter of paclitaxel liposome in rabbits. Methods The samples were extracted with methyl tert-butyl ether and separated on a C18 column with the mobile phase consisted of methanol：water = 65： 35. The internal standard was Diazepam. The wavelength was set at UV 227 nm. Results The standard curve was linear over the concentration range of 0.1 - 40.0 mg/L （ r = 0. 9997）. The method had a high extration recovery（ 〉 82.0% ） with the precision RSD of interday and intraday were less 6.0%. The method had been used in pharmacokinetic studies of paclitaxel-liposome in rabbits after iv 12 mg · kg^-1. The plasma paclitaxel concentration-time profile followed a hi-exponential disposion after analyzed by DAS2.0 software, t1/2α was 1.21 ±0.21 h, t1/2β was 33.56 ±6.69 h, Vd was 0. 81±0.09 L, CL was 0.04 ±0.01 L/h, AUC0-t was 321.11 ± 18.46 mg · h ^-1· L^-1 , AUC0→∞ was 722.20 ± 170.36 mg · h ^-1· L^-1 K10 was 0.04 ±0.01/h, K12 was 0.25 ± 0.04/h, K21 was 0.32 ±0.06/h. Conclusion The method is reliable, convenient, and more efficient, and can be applied to the determination of paclitaxel concentration in plasma and study of its pharmacokinetics in rabbits.

关 键 词：紫杉醇 脂质体 HPLC 药代动力学 

分 类 号：R969.1[医药卫生—药理学]