Evaluation of Red Ginseng-Drug Interaction by CYP450 Induction in High Dose Administration in Mice

Abstract

Abstract Objectives Ginseng–drug interactions at high doses of ginseng are poorly understood. Here we observed the possibility of herb–drug interaction between the Korean red ginseng (KRG) extract and cytochrome P450 (CYP) substrates in higher administration. Methods We determined the CYP activities in vivo after orally administration of KRG extract doses of 0.5, 1.0, and 2.0 g/kg for 2 or 4 weeks by monitoring the concentration of five CYP substrates/metabolites in the blood. Results The AUC for OH-midazolam/midazolam catalyzed by CYP3A was increased significantly by the administration of 2.0 g/kg KRG extract for 2 and 4 weeks. CYP3A-catalyzed midazolam 1ʹ-hydroxylation also increased significantly in a dose- and time-dependent manner in the S9 fraction of mouse liver which wasn't related to induction by transcription. Whereas CYP2D-catalyzed dextromethorphan O-deethylation decreased in a dose- and time-dependent manner in vivo. We observed interactions between KRG extract and CYP2D and CYP3A substrates at high KRG doses in mice. Conclusions Based on this result, patients may adhere to a daily recommended dose for ginseng products to avoid adverse drug effects. Funding Sources This work was supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry, and Fisheries (IPET) through the Export Promotion Technology Development Program, funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA, grant number 316,017–3) and the Korea Basic Science Institute (KBSI) National Research Facilities & Equipment Center (NFEC) grant funded by the Korea Government (Ministry of Education) (No. 2019R1A6C1010001).