伊立替康在免疫性肝损伤大鼠体内的药动学特征研究

 目的 探讨伊立替康(CPT-11)在免疫性肝损伤大鼠体内的药动学特征。方法 采用腹腔注射卡介苗（BCG）和脂多糖（LPS）建立大鼠免疫性肝损伤模型。模型组和正常对照组分别尾静脉注射伊立替康(20 mg·kg^-1)，于给药后不同时间点采血，采用HPLC测定血浆中伊立替康和代谢产物SN-38的浓度，计算药动学参数。结果 与正常大鼠相比，免疫性肝损伤大鼠体内伊立替康的AUC_{0-24 h} 、AUC_0-∞和ρ_max显著增加(P

The Pharmacokinetics of Irinotecan in Rats with Immunological Liver Injury

OBJECTIVE To investigate the pharmacokinetics of irinotecan(CPT-11) in SD rats with immunological liver injury.METHODS The animal model of immunological liver injury was established by intraperitoneal injection of lipopolysaccharide(LPS) plus Bacille-Calmette-Guerin(BCG) in rats.Rats were randomly divided into two groups: normal control group and immunological liver injury model group.The two groups were injected with CPT-11(20 mg·kg-1) via tail vein and plasma concentrations of CPT-11 and its metabolite SN-38 were determined by HPLC.Pharmacokinetical parameters were calculated.RESULTS Compared with the normal control group,AUC0-24 h,AUC0-∞ and ρmax of CPT-11 in immunological liver injury rats were increased significantly(P<0.05),but AUC0-24 h,AUC0-∞ and ρmax of SN-38 were decreased significantly(P<0.05).CONCLUSION Under the state of immunological liver injury,the hydrolysis of CPT-11 is inhibited significantly.The underlying mechanism may be related to the down-regulation of the expression of carboxylesterase 2 by LPS.