7-乙基-10-羟基喜树碱脂质体在大鼠体内的代谢和排泄

Metabolism and excretion of 7-ethyl-10-hydroxycamptothecin liposomes in rats

目的考察7-乙基-10-羟基喜树碱(SN-38)脂质体经静脉注射后,在大鼠尿液、粪便中的代谢产物以及以SN-38原形药物排泄的量。方法大鼠尾静脉单次给予2.77 mg/kg SN-38脂质体,分别于0~6、6~12、12~24、24~48 h分段收集尿液、粪便,采用UPLC/Q-TOFMS法对SN-38脂质体在大鼠尿液、粪便中的代谢产物进行鉴定,并且建立HPLC法,用于大鼠尿液及粪便样品中SN-38原形药物的排泄量的测定。结果 SN-38脂质体的在大鼠体内的代谢产物经鉴定为SN-38G。48 h内脂质体组共有1.57%的原形药物经过尿液排出,共有12.94%的SN-38原形药物经过粪便排出。结论 SN-38脂质体只有少部分以原形药物经尿液和粪便排出体外。

Objective To investigate the metabolism and excretion in urine and feces of rats after intravenous injection of 7-ethyl-10-hydroxycamptothecin(SN-38)liposomes.Methods SN-38 liposome of 2.77 mg/kg were iv administered to the tail vein of rats,collecting 48 h urine and feces in 0—6 h,6—12 h,12—24 h,24—48 h,respectively.UPLC/Q-TOF MS method was used to preliminarily identify the metabolites of SN-38 liposome in rat urine and feces,and HPLC method was established for the determination of the primary drug excretion of SN-38 in rat urine and feces.Results The metabolites of SN-38 liposome in rats were identified as SN-38G.A total of 1.57%of the original drug in the liposome group was excreted in the urine within 48 h,and a total of 12.94%of the SN-38 prototype drug was excreted through the feces.Conclusion Only a small part of the SN-38 liposome is excreted in urine and feces as the original drug.