肝靶向阿柔比星A聚氰基丙烯酸异丁酯毫微粒药物动力学研究  

Study on pharmacokinetics of aclarubicin A polyisobutylcyanoacrylate nanoparticles

作　　者：蒋学华[1] 廖工铁[1] 

机构地区：[1]华西医科大学药学院

出　　处：《中国抗生素杂志》1999年第1期35-38,共4页Chinese Journal of Antibiotics

基　　金：国家自然科学基金;国家科委医药技术创新博士项目

摘　　要：为提高阿柔比星（ａｃｌａｒｕｂｉｃｉｎＡ，ＡＣＲＡ）体内抗肝癌效果，降低其对正常组织器官的毒副作用，以氰基丙烯酸异丁酯（ｉｓｏｂｕｔｙｌｃｙａｎｏａｃｒｙｌａｔｅ，ＩＢＣ）为载体材料，制备出肝靶向阿柔比星Ａ聚氰基丙烯酸异丁酯毫微粒（ａｃｌａｒｕｂｉｃｉｎＡｐｏｌｙｉｓｏｂｕｔｙｌｃｙａｎｏａｃｒｙｌａｔｅｎａｎｏｐａｔｉｃｌｅｓ，ＡＣＲ－ＩＢＣ－ＮＰ）。以３Ｈ－ＡＣＲＡ为示踪物，采用液体闪烁计数技术研究了ＡＣＲ－ＩＢＣ－ＮＰ灌胃与尾静脉注射两种给药途径在小鼠血液及靶器官肝脏中的药物动力学规律。结果表明，灌胃给药时ＡＣＲ－ＩＢＣ－ＮＰ在血液与肝脏中的药时数据均可以用血管外给药的二室模型描述：尾静脉注射给药时ＡＣＲ－ＩＢＣ－ＮＰ在血液与肝脏中的药时数据虽然可以分别用二室模型与血管外给药的二室模型进行较好地描述，但是，靶向至肝脏的ＡＣＲ－ＩＢＣ－ＮＰ作为药物储库，使血液中药时曲线出现双峰，常规药物动力学模型均不能很好地拟合，提示具靶向缓释特点的药物传输系统的药物动力学模型有待进一步研究。ＡＣＲ－ＩＢＣ－ＮＰ的体内过程表明，ＡＣＲ－ＩＢＣ－ＮＰ在尾静脉注射与灌胃两种给药途径时均具有肝靶向作用与缓释作用。以靶向效率（?Aclarubicin A polyisobutylcyanoacrylate nanoparticles (ACR IBC NP) was a liver targeting drug delivery system for increasing antihepatoma effect and reducing toxicity of aclarubicin A (ACR). The pharmacokinetic characteristics of aclarubicin polyisobutylcyanoacrylate nanoparticles (ACR IBC NP) in mice blood and liver after injection via mice tail vein and oral administration were described in this paper. 3 H as a tracer isotope was labelled in aclarubicin ( 3H ACR). The radioactivity of blood and liver were determined by liquid scintillation counting technique. The pharmacokinetic parameters of ACR IBC NP were obtained by using 'Practical Pharmacokinetic Program. 3P87' in IBM PC computer. The results showed that the data of concentration time of ACR IBC NP in mice blood and liver iv administration can be established by two compartment model with iv injection and two compartment model with first order absorption respectively and the data of concentrations-time of ACR IBC NP in mice blood and liver after po administration can be established by two compartment model with lag time and first order absorption and two compartment model with no lag time and first order absorption respectively. Between the change process of ACR IBC NP in blood and in liver have a relationship. The targeting effect and the bioavailability after oral administrated of targeting drug delivery system can be evaluated by targeting efficiency 'TE' and targeted organ bioavailability respectively. TE of ACR IBC NP were 14.41 and 28.47 after iv and po administration respectively. The targeted organ bioavailability of ACR IBC NP was 76.10%.

关 键 词：阿柔比星A 毫微粒 药物动力学 

分 类 号：R978.1[医药卫生—药品]