沙利度胺对伊立替康及其代谢物SN-38在大鼠体内药动学的影响

目的:研究伊立替康合用沙利度胺后伊立替康及其代谢物SN-38在大鼠体内的药动学情况。方法:以健康♂SD大鼠为受试对象,随机分成伊立替康注射液10、20mg·kg-1单用组(对照组)及与沙利度胺(20mg·kg-1)合用组(实验组),给药后0.083、0.5、1.0、2.0、4.0、6.0、8.0、10、12h采集血样并测定伊立替康、SN-38血药浓度,采用DASver2.0软件拟合二者的药动学参数。结果:与对照组比较,伊立替康10mg·kg-1实验组伊立替康AUC0～t、Cmax显著增加(P<0.05),SN-38的AUC0～t降低(P<0.05);20mg·kg-1实验组伊立替康Cmax显著增加(P<0.05),SN-38的Cmax、AUC0～t显著降低(P<0.05)。结论:联用沙利度胺可以增加伊立替康AUC0～t同时减少SN-38的AUC0～t及Cmax。

Effect of Thalidomide on Pharmacokinetics of Irinotecan and SN-38 in Rats

OBJECTIVE： To study pharmacokinetics of irinotecan and its metabolite SN-38 in rats after administration of irinotecan and thalidomide.METHODS： Healthy male SD rats were randomized to given 10 mg·kg-1 irinotecan and 20 mg·kg-1 irinotecan （control group） or irinotecan combined with 20 mg·kg-1 thalidomide （trial group）.Blood samples were collected at 0.083 h,0.5 h,1.0 h,2.0 h,4.0 h,6.0 h,8.0 h,10 h and 12 h after medication.The plasma concentrations of irinotecan and SN-38 were determined and pharmacokinetic parameters were calculated using DASver2.0 software.RESULTS： As compared with control group,AUC0～t and Cmax of irinotecan in 10 mg·kg-1 irinotecan trial group were increased significantly （P0.05） while AUC0～t of SN-38 was decreased （P0.05）;in 20 mg·kg-1 irinotecan trial group the Cmax of irinotecan was increased strikingly （P0.05） while the Cmax and AUC0～t of SN-38 were decreased remarkably （P0.05）.CONCLUSION： Thalidomide combined with irinotecan can increase the AUC0～t of irinotecan and decrease the Cmax and AUC0～t of SN-38.