伊立替康与人参的相互作用研究

Herb-drug Interaction Between Ginseng Radix et Rhizomn and Irinotecan

关键词:  伊立替康  7-乙基-10-羟基喜树碱  人参  相互作用  药动学

Key words:  irinotecan  7-ethyl-10-hydroxycamptothecin  Ginseng Radix et Rhizomn  interaction  pharmacokinetics

摘要:

目的 考察联用人参对伊立替康大鼠体内药动学的影响，研究伊立替康与人参的相互作用。方法 将SD大鼠随机分成3组：长期组、单剂量组和对照组。长期组人参提取液连续灌胃给药7 d，单剂量组人参提取液灌胃给药1次，对照组给予同体积生理盐水，3组均最后1次给药0.5 h后尾静脉注射伊立替康，于给药后不同时间点取血，采用UPLC-MS/MS测定大鼠血浆中伊立替康以及活性代谢产物7-乙基-10-羟基喜树碱的浓度，并以DAS 3.1软件计算药动学参数，用SPSS 21.0做统计分析。结果 伊立替康长期组主要药动学参数：t_1/2（0.933±0.080）h、AUC_0-t（3.337±0.341）μg.h.L^–1、MRT_0-t（0.541±0.013）h、MRT_0-∞（0.572±0.016）h；单剂量组：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：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、MRT_0-∞（0.391±0.026）h。7-乙基-10-羟基喜树碱长期组主要药动学参数：t_1/2（1.240±0.094）h、AUC_0-t（7.810±0.252）μg.h.L^–1、MRT_0-t（2.141±0.031）h、MRT_0-∞（2.250±0.057）h；单剂量组：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、MRT_0-∞（2.408±0.089）h；对照组：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、MRT_0-∞（1.935±0.066）h。与对照组相比，长期组伊立替康的t_1/2、MRT_0-t、MRT_0-∞显著延长（P<0.05）；7-乙基-10-羟基喜树碱则单剂量组的t_1/2显著延长（P<0.05）。结论 人参使用1周后联用伊立替康，大鼠体内伊立替康的血浆半衰期、平均滞留时间明显提高。

Abstract:

OBJECTIVE To study the interaction between irinotecan and Ginseng Radix et Rhizomn by measuring the effect of ginseng on the pharmacokinetics of irinotecan in rats. METHODS SD rats were randomly divided into three groups:the long-term group, single dose group and the control group. In the long-term group, the extract of ginseng was administrated for 7 d continuously; the extract of Ginseng Radix et Rhizomn extract was administrated once in the single dose group, and normal saline was administrated in the control group. Irinotecan was injected by tail vein 0.5 hour after the last administration in the 3 groups and blood was taken at different time points after administration. The plasma concentrations of irinotecan and its active metabolite 7-ethyl-10-hydroxycamptothecin were determined by UPLC-MS/MS method, and the pharmacokinetic parameters were calculated by DAS 3.1 software, and analyzed by SPSS 21.0. RESULTS The main pharmacokinetic parameters of irinotecan in the long-term group:t_1/2(0.933±0.080)h, AUC_0-t(3.337±0.341)μg.h.L^-1, MRT_0-t(0.541±0.013)h, MRT_0-∞(0.572±0.016)h; single dose group: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; control group: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, MRT_0-∞(0.391±0.026)h. The main pharmacokinetic parameters of 7-ethyl-10-hydroxycamptothecin in the long-term group:t_1/2(1.240±0.094)h, AUC_0-t(7.810±0.252)μg.h.L^-1, MRT_0-t(2.141±0.031)h, MRT_0-∞(2.250±0.057)h; single dose group: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, MRT_0-∞(2.408±0.089)h; control group: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, MRT_0-∞(1.935±0.066)h. Compared with the control group, the t_1/2, MRT_0-t and MRT_0-∞of irinotecan were significantly prolonged in the long-term group(P<0.05), while the t_1/2 of 7-ethyl-10-hydroxycamptothecin was significantly prolonged in the single dose group(P<0.05). CONCLUSION The plasma half-life and mean residence time of irinotecan in rats were significantly increased after one week's use of Ginseng Radix et Rhizomn.