聚乙二醇化盐酸多柔比星脂质体注射液药代动力学的对比研究

A Comparison of Pharmacokinetics of PEGylated Liposomal Doxorubicin Hydrochloride Injections

为了评价盐酸多柔比星脂质体受试制剂(S)和进口同规格参比制剂(R)的一致性,对比研究了2种制剂单次静脉注射后,在SD大鼠和荷人卵巢癌A-2780肿瘤裸鼠的血清和不同组织内的药物浓度。建立了HPLC-FLD法,用于测定SD大鼠血清、荷瘤裸鼠血清和肿瘤中多柔比星(1)总含量(即游离1和PEG化脂质体中1的含量总和)和PEG化脂质体中1含量,以及大鼠不同组织中1的总含量。结果显示,两种制剂以5 mg/kg的剂量,尾静脉注射给予SD大鼠,给药后1 h、24 h和72 h,分别对9个组织脏器中的1总含量进行双单侧检验分析,在P=0.05水平上2种制剂的差异不显著;2种制剂以10 mg/kg的剂量,尾静脉注射给予荷瘤裸鼠,给药后1 h、24 h和72 h分别对瘤内1总含量和PEG化脂质体中1含量进行双单侧检验分析,在P=0.05水平上2种制剂的差异也不显著。由此推断,受试制剂与参比制剂在动物体内的分布无统计学差异。

This paper aimed to study the distribution of PEGylated liposomal doxorubicin （PLD） hydrochloride injection in different tissues of SD rats and A-2780 tumor-bearing nude mice after single dose intravenous administration with the marketed similar foreign preparation as control, and provide supports for follow-up studies. An analytical method had been established for determining the concentrations of doxorubicin （1）, 1 in PLD and their total value in rat serum, nude mouse serum and tumors as well as 1 in rat tissues. After intravenous administration of test preparation or reference preparation to SD rats at dose of 5 mg/kg, the total concentrations of 1 in nine tissues （heart, liver, spleen, lung, kidney, brain, intestinal, marrow and skin）, including free ones and liposomes, at time points of 1, 24 and 72 h were determined. Besides, the total concentrations of 1 and 1 in PLD in tumors of A-2780 tumor-bearing nude mice treated with PLD injection at different time points of 1, 24 and 72 h were also determined. The results showed that there were no statistic differences between test and reference PLD injections in 1 distribution in nine tissues of SD rats as well as in tumors of nude mice at the 0.05 level. It was concluded that there was no statistic difference in the distribution of test preparation and reference product in animals.