SN-38脂质体的药动学及组织分布学特征

发布时间：2018-02-26 21:55

  本文关键词： SN-脂质体 药动学 组织分布 伊立替康　出处：《沈阳药科大学学报》2016年04期 　论文类型：期刊论文

【摘要】：目的研究SN-38脂质体大鼠体内药动学及小鼠组织分布学特征,为进一步非临床研究提供一定的实验基础。方法以盐酸伊立替康注射液(irinotecan,简称CPT-11)为参比制剂,大鼠尾静脉单次给予不同剂量的SN-38脂质体,于不同时间点眼框取血;小鼠尾静脉给予单剂量的SN-38脂质体,于2 h处死,取心、肝、脾、肺、肾等组织匀浆。并且建立HPLC法,用于大鼠血浆及小鼠组织样品中SN-38的含量测定。结果低、中、高3种剂量的SN-38脂质体在大鼠体内均消除较快,其t1/2无明显差异,AUC则随剂量的增加而增加。小鼠尾静脉注射SN-38脂质体后,主要聚集在肝、脾、肺中,且其在心、肾组织中的含量低于对照组。结论 SN-38脂质体在大鼠体内呈线性动力学消除。小鼠组织分布结果表明其对于肝、脾等网状内皮细胞丰富的组织靶向性强,能够提高该器官的治疗指数;同时还可降低对心、肾组织的毒性及不良反应。
[Abstract]:Objective to study the pharmacokinetics and histological distribution of SN-38 liposome in rats, and to provide an experimental basis for further non-clinical study. Methods Iritikang Hydrochloride injection (CPT-11) was used as a reference preparation. Rat caudal vein was given single dose of SN-38 liposome, and blood was taken from eye frame at different time points, and mice were given single dose of SN-38 liposome for 2 h. The homogenate of heart, liver, spleen, lung, kidney and so on were taken, and the HPLC method was established. It was used to determine the content of SN-38 in rat plasma and tissue samples of mice. The results showed that SN-38 liposomes of low, medium and high doses were eliminated rapidly in rats. There was no significant difference in t1 / 2 and AUC was increased with the increase of dose. After caudal vein injection of SN-38 liposome, it was mainly concentrated in liver, spleen, lung, and heart. Conclusion SN-38 liposomes were eliminated linearly in rats. The tissue distribution in mice showed that the liposomes were highly targeted to the liver, spleen and other reticuloendothelial cells. It can improve the therapeutic index of the organ and decrease the toxicity and adverse reaction to heart and kidney.
【作者单位】： 沈阳药科大学药学院;本溪高中;
【分类号】：R965
，

本文编号：1539828