7-乙基-10-羟基喜树碱脂质体在大鼠体内的代谢和排泄

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。

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

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.