人参总皂苷对伊立替康及其代谢产物在大鼠体内药动学的影响

Effects of Total Saponin of Ginseng(Panax ginseng C.A.Meyer)on Pharmacokinetics of Irinotecan and Its Derivative in Rats

目的研究人参总皂苷对伊立替康及其代谢产物在大鼠体内药动学的影响。方法将SD大鼠随机分成实验组与对照组,实验组灌胃人参总皂苷400 mg·kg^(-1),0.5 h后尾静脉注射伊立替康20 mg·kg^(-1);对照组同法给予0.9%氯化钠溶液与等剂量伊立替康。给药后不同时间点取血,采用超高效液相色谱-串联质谱法测定大鼠血浆伊立替康及其活性代谢产物7-乙基-10-羟基喜树碱(SN-38)浓度,以DAS3.1版软件计算药动学参数,SPSS 21.0版软件行统计分析。结果实验组伊立替康主要药动学参数t_(1/2)(5.527±1.156)h、AUC_(0-t)(2.078±0.118)μg·h·L^(-1)、MRT_(0-t)(0.462±0.023)h、MRT_(0-∞)(1.405±0.212)h;对照组伊立替康主要药动学参数t_(1/2)(0.296±0.011)h、AUC_(0-t)(2.161±0.146)μg·h·L^(-1)、MRT0-t(0.360±0.026)h、MRT_(0-∞)(0.391±0.026)h;实验组SN-38主要药动学参数t_(1/2)(1.398±0.045)h、AUC_(0-t)(9.073±0.109)μg·h·L^(-1)、MRT0-t(2.337±0.081)h、MRT_(0-∞)(2.408±0.089)h;对照组SN-38主要药动学参数t_(1/2)(0.928±0.050)h、AUC_(0-t)(8.933±0.434)μg·h·L^(-1)、MRT0-t(1.869±0.061)h、MRT_(0-∞)(1.935±0.066)h。与对照组比较,实验组SN-38 t_(1/2)延长,差异有统计学意义(P<0.05)。结论合用人参总皂苷后,大鼠体内伊立替康活性代谢产物SN-38血浆半衰期延长。

Objective To study the pharmacokinetics effect of total saponin of ginseng(Panax ginseng C.A.Meyer)on irinotecan and its derivative in rats.Methods SD rats were randomly divided into an experimental group and a control group.Total saponin of ginseng(400 mg·kg^(-1))was given to the experimental group once,and then irinotecan 20 mg kg^(-1) was injected into the tail vein half an hour later.Normal saline and irinotecan were given to the control group in parallel.The blood was taken at different time points after administration.The plasma concentrations of irinotecan and its active metabolite SN-38 were determined by the ultra performance liquid chromatography-tandem mass spectrometer(UPLC-MS/MS)method,and the pharmacokinetic parameters were calculated by DAS 3.1 software.The results were analyzed by SPSS 21.0 statistical software.Results The main pharmacokinetic parameters of irinotecan in the experimental group were as followed:t_(1/2)=(5.527±1.156)h,AUC_(0-t)=(2.078±0.118)μg·h·L^(-1),MRT_(0-t)=(0.462±0.023)h,and MRT_(0-∞)=(1.405±0.212)h.The main pharmacokinetics parameters of irinotecan in control group were as followed:t_(1/2)=(0.296±0.011)h,AUC_(0-t)=(2.161±0.146)μg·h·L^(-1),MRT_(0-t)=(0.360±0.026)h,and MRT_(0-∞)=(0.391±0.026)h.The main pharmacokinetic parameters of SN-38 in experimental group were as followed:t_(1/2)=(1.398±0.045)h,AUC_(0-t)=(9.073±0.109)μg·h·L^(-1),MRT_(0-t)=(2.337±0.081)h,and MRT_(0-∞)=(2.408±0.089)h.And those of SN-38 in control group were as followed:t_(1/2)=(0.928±0.050)h,AUC_(0-t)=(8.933±0.434)μg·h·L^(-1),MRT_(0-t)=(1.869±0.061)h,and MRT_(0-∞)=(1.935±0.066)h.Compared with the control group,the t_(1/2) of SN-38 in the experimental group were significantly prolonged(P<0.05).Conclusion When the total saponin of ginseng is combined with irinotecan,the t_(1/2) of SN-38 can significantly increased in rats.