埃博霉素B的大鼠体内药动学及组织分布  

Pharmacokinetics and Tissue Distribution of Epothilone B in Rats

作　　者：徐智儒[1] 肖璘[1] 廖建维 代常亮 秦燕[1] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院,创新药物与制药工艺国家重点实验室,上海200040 [2]浙江海正药业股份有限公司,浙江台州318000

出　　处：《中国医药工业杂志》2012年第5期363-367,共5页Chinese Journal of Pharmaceuticals

摘　　要：分别建立了液相色谱-质谱法和高效液相色谱法测定大鼠血浆和组织中的埃博霉素B,并考察该化合物在大鼠体内的药动学及组织分布情况。大鼠按3个剂量(0.5、1和2 mg/kg)静脉给药后测定不同时间点的血浆浓度,数据经拟合处理,符合二室开放模型特征,主要药动学参数如下:t1/2(7.17±0.68)、(7.65±1.40)和(6.68±0.36)h,AUC0→t(60.4±6.5)、(160.4±37.8)和(428.8±67.1)ng.ml-1.h。荷瘤Wistar大鼠1 mg/kg静脉给药后,于不同时间点测定各组织药物浓度,结果显示药物迅速从血浆分布到组织,并且在肿瘤中的滞留时间较长。The validated LC-MS and HPLC method were developed for the determination of epothilone B in rat plasma and tissue,respectively.The pharmacokinetic properties of epothilone B were examined after a single iv injection of 0.5,1 and 2 mg/kg to rats,respectively.The results suggested that the pharmacokinetic properties of epothilone B fitted well into a two-compartment open model with t1/2β of（7.17±0.68）,（7.65±1.40） and（6.68±0.36）h,and AUC0→t of （60.4±6.5）,（160.4±37.8） and（428.8±67.1）ng·ml-1·h according to the single dose of 0.5,1 and 2 mg/kg,respectively.A single dose（1 mg/ml） of epothilone B to tumor bearing Wistar rats resulted in a very rapid wide distribution from plasma to tissue.Plasma elimination was very rapid,while the elimination in tumor was rather slow.

关 键 词：埃博霉素B 药动学 组织分布 液相色谱-质谱 高效液相色谱 测定 

分 类 号：R969[医药卫生—药理学] O657.72[医药卫生—药学]