4-4″-(2″,2″,6″,6″-四甲基哌啶氮氧自由基)氨基-4′-去甲表鬼臼毒素在荷肉瘤180小鼠体内的药物动力学

摘要

目的:研究4-[4″-(2″,2″,6″,6″-四甲基哌啶氮氧自由基)氨基]-4′-去甲表鬼臼毒素在荷肉瘤180小鼠体内的药物动力学.方法:用HPLC紫外检测法.结果:GP-7在小鼠血浆中的浓度-时间过程符合二室开放模型.20,60mg·kg-1iv,T1/2β约40 min;药物浓度以肝脏和肺中最高;肿瘤组织中药物水平高于脾,肾和骨髓.72 h内,经尿以原形排出的GP-7占给药量的20%左右.结论:GP-7在荷肉瘤180在小鼠体内分布较广,消除较慢.肿瘤组织中浓度较高,部分以原形从尿中排出.%AIM: To study the pharmacokinetics of 4-[4″- (2″, 2″, 6″, 6″-tetramethyl-1″-piperindyloxy) amino ]-4 ′ -demethylepipodophyllotoxin (GP-7) in mice bearing sarcoma 180.METHOD: Using HPLC with a uv detector at 285 nm. RESULTS: The plasma concentration-time course of GP-7 in mice was best fitted to a 2-compartment open modle after iv 20, 60 mg·kg-1. At both doses the plasma T1/2β was around 40 min. The highest concentration was found in liver and lung. The level of GP-7 was higher in tumor than in kidney,for 10 d. Urinary excretion of GP-7 as unchanged drug accounted for about 20 % of the administered doses 72 h after injection. CONCLUSION: GP-7 disappeared more slowly from the plasma of mice bearing sarcoma 180,distributed extensively over the tissues and was partially excreted from urine. The concentrition of GP-7 in tumor was higher.