摘要
目的:观察注射用纳米羟基喜树碱(HCPT纳米针)静脉推注后在家兔血浆药物浓度随时间变化趋势和药动学参数以及小鼠体组织分布特征。方法:建立HPLC检测家兔血浆和小鼠各组织中羟基喜树碱含量的方法;绘制3个剂量组(2.5、5.0、7.5mg/kg)家兔血浆药-时曲线并采用3p97软件模拟房室模型并计算药动学参数;BALB/c小鼠给予HCPT纳米针(10mg/kg)后,检测15min、1h和2h各组织和血浆中羟基喜树碱的含量。结果:1)HCPT纳米针家兔耳静脉单次给药符合1/C2权重的三室模型,AUC和Vd等药动学参数在既定药物浓度范围内呈线性改变。2)HCPT纳米针在肝组织中浓度最高,分布顺序:肝>肾>脾>肠>胃>肺>心。3)HCPT纳米针给药后在肝组织保留时间长。结论:HCPT纳米针在肝组织中药物浓度高、存留时间长,具有明确的靶向性。
Objective： To investigate the rabbit＇s blood drug level and pharmacokinetics （PK） parameter of 10-hydroxycamptothec （HCPT） nanoparticle injection and to detected the tissue distribution performance in mice. Methods： HCPT in plasma and tissues was quantitated by reversed-phase HPLC and UV detector. EXCEL software was used in drawing the plasma concentration-time curves, and 3p97 software was used in calculation of compartment model and PK parameters. HCPT nanoparticle injection was administered to BALB/c mice by bolus injection at dose of 10mg·kg^-1 body weight. Drug levels in various tissues was detected at post injection time of 15, 60 and 120 min. Results： a, the concentration-time profile for HCPT nanoparticle injection could be best described by three-compartment model, and the PK parameter transformed following the dose ascend in a certain range; b, the highest concentration of HCPT nanoparticle injection was obtained in liver, and the sequence of HCPT levels in various tissues was： liver〉kidney〉spleen〉stomach〉 lung〉heart; c, HCPT nanoparticle injection was obviously accumulated in liver. Conclusion： HCPT nanoparticle injection can be distributed into organs more extensively and can reflect great liver targeting capability.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2005年第19期1116-1119,共4页
Chinese Journal of Clinical Oncology
关键词
抗肿瘤药
喜树碱纳米技术
药代动力学
组织分布
羟基喜树碱
Antineoplastic agent
Camptothecin nanotechnology
Pharmacokinetics
Tissue distribution
10-hydroxycamptothec
