Study on the Effects of Radix Adenophorae Coadministrated with Veratrum nigrum L on Cytochrome P450 Subtype Enzymes Activities of Rats by Cocktail Approach Using Probe Drugs

Chinese Journal of Pharmacovigilance ›› 2013, Vol. 10 ›› Issue (5): 257-262.

Study on the Effects of Radix Adenophorae Coadministrated with Veratrum nigrum L on Cytochrome P450 Subtype Enzymes Activities of Rats by Cocktail Approach Using Probe Drugs

ZHU Guan-xiu^1,2 ,WANG Yu-guang^2*, LI Fei² ,MA Zeng-chun² ,LIANG Qian-de² ,XIAO Cheng-rong² ,TAN Hongling² ,TANG Xiang -lin², ZHANG Bo -li² ,GAO Yue^2*

1.School of Pharmacy, Central South University, Hunan Changsha 410008, China;
2.Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China;3Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China

Received:2013-03-12 Revised:2016-03-09 Online:2013-05-08 Published:2016-03-09

Abstract

Abstract: Objective To determine the influence of Radix Adenophorae Coadministrated with Veratrum nigrum L . on cytochrome P450 isoforms CYP1A2,CYP3A4, CYP2C9 and CYP2C19 by Cocktail probe drugs in rats, thus explore the in vivo evidence of the imcompatibility of them from the perspective of drug -drug interactions. Methods 24 male wistar rats were randomly divided into Radix Adenophorace group, Veratrum nigrum L., combined group and blank control group, which were given Radix Adenophorace decoction(13.5g·kg^-1), Veratrum nigrum L. decoction (0.81g·kg^-1), co-decoction(14.31g·kg^-1) and normal saline for 7 days, then injected the mixture of4 probes through vena caudalis on the 8th day, and soon after the blood samples were obtained through extirpating the eyeballs at a series of time-points. HPLC method was used to determine the concentrations of probe drugs in rat plasma, and pharma-cokinetic parameters were estimated by WinNolin5.2. The effects of test drugs on the activities of cytochrome P450 isoforms were judged indirectly by comparing the pharmacokinetic parameters of treated groups with those of control group. Results Compared with the blank control group, Veratrum nigrum L. was decreased AUC(0～t) of tolbutamide and increased its Vz; Radix Adenophorae were decreased AUC(0～∞) of caffeine, significantly decreased AUC(0～t), AUC(0～∞) of tolbutamide, and was increased Vz, CL of tolbutamide, no significant difference of dapsoneand omeprazole. Compared with the Veratrum nigrum L. group, combination could increase MRT(0～t) of dapsone,decrease AUC(0～t), AUC(0～∞) of omeprazoleand, increase CL of it; Compared with the Radix Adenophorae group,combination could increase AUC(0～t) of omeprazole. Conclusion Compared with the blank control group,. can induce CYP2C19 activities; Radix Adenophorae can induce CYP1A2 and CYP2C9 activities significantlywith no effect on the activities of CYP3A4 and CYP2C19. Compared with the Veratrum nigrum L. group, CYP3A4 activities were inhibited in combined groups, and CYP2C19 activities were induced with no effects on the activities of CYP1A2 and CYP2C9. Compared with the Radix Adenophorae group, combination can inhibit the activities of CYP2C19.

Key words: Cocktail, Radix Adenophorae , Veratrum nigrum L., eighteen imcompatible medication, CYP450, probe drugs

CLC Number:

R285
R963

ZHU Guan-xiu ,WANG Yu-guang, LI Fei ,MA Zeng-chun ,LIANG Qian-de ,XIAO Cheng-rong ,TAN Hongling ,TANG Xiang -lin, ZHANG Bo -li ,GAO Yue. Study on the Effects of Radix Adenophorae Coadministrated with Veratrum nigrum L on Cytochrome P450 Subtype Enzymes Activities of Rats by Cocktail Approach Using Probe Drugs [J]. Chinese Journal of Pharmacovigilance, 2013, 10(5): 257-262.

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