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PEG化脂质体多柔比星在动物体内的药动学及组织分布 被引量:8

Pharmacokinetics and Tissue Distribution of PEGylated Liposomal Doxorubicin in Animals
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摘要 比较研究了PEG化脂质体多柔比星(阿霉素)受试制剂与进口同类参比制剂静注后,在动物体内的药动学及组织分布。采用HPLC法测定Beagle犬的血药浓度和荷瘤(Walker256)Wistar大鼠各组织药物浓度。结果显示,Beagle犬静注1mg/kg受试制剂及参比制剂后,药动学参数分别为t1/2β23.0和23.5h,表观分布容积0.060和0.062L/kg,AUC0-∞500.29和531.57μg·ml-1·h,多柔比星在犬体内的药代动力学过程均符合二室模型的特征。荷瘤(Walker256)Wistar大鼠静注5mg/kg受试制剂及参比制剂后,脾中含量最高,其次为肿瘤、小肠、肝,皮肤中含量最低。统计学分析显示,两制剂在犬体内主要药动学参数及大鼠组织肝、心、脾、肾、小肠、皮肤和肿瘤内的分布,无显著性差异(P>0.05)。 The pharmacokinetics and tissue distribution of prepared PEGylated liposomal doxorubicin (test preparation) and imported product (reference preparation) in animals were studied. After iv test and reference preparation, the concentrations of doxorubicin in Beagles dog plasma and Wistar rat with tumor Walker-256 tissues were determined by HPLC. The results showed that after a single iv administration 1 mg/kg test and reference preparation to Beagle dogs, the pharmacokinetic parameters were as follows: t1/2β 23.0 and 23.5 h, Vd 0.060 and 0.062 L/kg, AUC0-∞ 500.29 and 531.57 ug·ml^-1·h. It was fitted two-compartment model. And after a single iv administration 5 mg/kg test and reference preparation to Wistar rats (with tumor Walker-256), the concentration of doxorubicin was highest in spleen, and then in tumor, small intestine, liver. It was lowest in skin. The statistics analysis showed that there was no significant difference (P〉0.05) between the test and reference preparation in major pharmacokinetic parameters in dogs and tissue distribution in rats.
出处 《中国医药工业杂志》 CAS CSCD 北大核心 2009年第8期596-599,共4页 Chinese Journal of Pharmaceuticals
关键词 多柔比星 PEG化脂质体 药动学 组织分布 doxorubicin PEGylated liposomal pharmacokinetics tissue distribution
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参考文献6

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