Herb-drug Interaction Between Ginseng Radix et Rhizomn and Irinotecan

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.