新型抗肿瘤药物LS-177在大鼠体内的排泄研究

Excretion of a Novel Anticancer LS-177 in Rats

目的研究LS-177在大鼠体内的排泄情况。方法建立快速、灵敏的UPLC-MS/MS分析方法测定单次灌胃给予50.0mg·kg^(-1)的LS-177混悬液后,LS-177原型药物自雄雌大鼠尿液、胆汁和粪便中的排泄量。结果大鼠灌胃给药后,尿液96 h内、胆汁24 h内的累积排泄百分率具有明显的雌雄差异(P<0.05),粪便96 h内的雌雄差异不明显(P>0.05)。结论原型药物在尿液、胆汁和粪便中总的回收量约占给药剂量的50%,其中主要是由粪便排出体外,推测LS-177口服吸收差是其生物利用度低的主要原因。

OBJECTIVE To study the excretion profile of LS-177 in rats. METHODS A selective, sensitive and accurate UP- LC-MS/MS assay was developed and validated for the determination of LS-177 in rat urine, bile and feces. RESULTS After oral ad- ministration of LS-177 oral suspension at the dose of 50 mg· kg-1 , there was significant difference in the excretion percentages of LS- 177 between male and female rats both in urine and bile. No significant difference was observed in the excretion of LS-177 through fe- ces. CONCLUSION The data suggests that unabsorbed LS-177 excretion in feces is the main excretion pathway, indicating that poor oral absorption is the main cause of low bioavailability.