两种紫杉醇注射剂在荷瘤小鼠体内药动学与组织分布的比较研究

目的比较以聚氧乙烯蓖麻油为增溶剂的紫杉醇注射液（Taxol）与以白蛋白为载体的紫杉醇纳米注射剂（ABI）在荷瘤小鼠体内药动学及组织分布的差异。方法 BALB/c小鼠经前肢腋下皮下接种鼠源乳腺癌EMT6细胞,待瘤体长到约1 g,按既定分组经尾静脉分别给予Taxol和ABI,给药剂量以紫杉醇计均为20 mg.kg-1。HPLC-UV测定血浆、瘤组织及心、肝、脾、肺、肾等主要组织器官中紫杉醇含量,并计算相应药动学参数。结果 ABI组动物瘤组织中的紫杉醇AUC高于Taxol组23.3%,而血浆中紫杉醇的AUC则显著低于Taxol组,并具有更大的Vd和CL（P〈0.05）。两种不同制剂给药,紫杉醇在心、肝、脾、肾中的分布趋势基本一致,但ABI组动物肺中的紫杉醇分布显著低于Taxol组（P〈0.05）。结论和传统紫杉醇注射液相比,白蛋白紫杉醇纳米粒制剂的瘤组织分布靶向性和药动学特性显著改善,应用前景广阔。

Comparative Study on Pharmacokinetics and Tissue Distribution of Two Paclitaxel Injection Formulations in Tumor-bearing Mice

OBJECTIVE To compare the pharmacokinetic characteristics of paclitaxel formulated in Cremophor ethanol (Taxol) with that formulated as an albumin-bound nanoparticle (ABI) in tumor-bearing mices. METHODS ABI and Taxol were intravenously administrated with the same dosage of paclitaxel to tumor-bearing BALB/c mices, and then pharmacokinetic profiles of paclitaxel were investigated by determining drug concentration in plasma and tumor, and vital tissues including heart, liver, spleen, lung, and kidney with HPLC. RESULTS The group administrated with ABI showed a significantly lower AUC of paclitaxel in plasma and greater Vd and CL. However, the AUC of paclitaxel in tumor was 23.3% higher for ABI than that for Taxol (P < 0.05). The two groups had similar distribution profiles in vital tissues except that paclitaxel concentration in lung was much higher in the group of Taxol. CONCLUSION When compared with the conventional paclitaxel injection formulated in Cremophor ethanol, albumin-bound nanoparticle of paclitaxel showed better pharmacokinetic and tumor-targeting properties.