注射用纳米羟基喜树碱与普通粉针在家兔体内的药代动力学比较研究

Pharmacokinetics comparison between 10-hydroxycamptothecin nanoparticle injection and common injection in rabbits

目的:考察注射用纳米羟基喜树碱静脉推注给药后,家兔血浆药物浓度随时间变化趋势和药代动力学参数,并与注射用羟基喜树碱进行比较,评价纳米针药动学特性。方法:建立HPLC检测家兔血浆中羟基喜树碱含量的方法,采用3p97药代动力学计算软件模拟房室模型并计算药代动力学参数。结果:注射用羟基喜树碱家兔耳静脉单次推注给药符合1 C2 权重的二室模型,而注射用纳米羟基喜树碱符合1 C2 权重的三室模型。注射用羟基喜树碱的血浆Cmax是同剂量纳米针的3倍,AUC也是纳米针的2～3倍。同剂量下HCPT纳米针组Vc 均大于粉针组。纳米针消除半衰期(T1 2 β)较冻干粉针延长。结论:注射用纳米羟基喜树碱在家兔体内的药动学特性与普通粉针比较发生显著变化。

AIM: To investigate the pharmacokinetics (PK) of 10-hydroxycamptothec (HCPT) nanoparticle injection iv by comparing with the HCPT common injection in rabbits. METHODS: HCPT in plasma were quantitated by reversed-phase HPLC and UV detector. 3p97 software was used in calculation of compartment model and PK parameters. RESULTS: The concentration-time profile of HCPT nanoparticle injection was best described by three-compartment model, and the common injection was described by two-compartment model. Plasma peak concentration (C_ max) of HCPT common injection was three times as many as that of nanoparticle injection in equal dosage. Area under curve (AUC) of HCPT common injection was twofold higher than that of nanoparticle injection. Apparent volume of distribution of central compartment (V_c) of HCPT nanoparticle injection was greater than that of nanoparticle injection in equal dosage. HCPT nanoparticle injection had a longer elimination half life (T_ 1/2β) than that of common injection. CONCLUSIOM: The blood drug concentration and PK characteristic of HCPT nanoparticle injection were very different from HCPT common injection in rabbits.