Evaluation of drug–drug interactions of traditional Japanese medicines (Hochuekkito, Goreisan and Ninjin’yoeito) in CYP3A-humanised mice

Traditional Japanese medicines (Kampo medicines) are increasingly used concurrently with other medications, but evidence regarding their potential for drug-drug interactions (DDIs) is insufficient. Given the important role of cytochrome P450 3A (CYP3A) in DDIs, this study assessed the CYP3A-mediated DDI risk of three Kampo medicines (Hochuekkito, Goreisan and Ninjin'yoeito).We utilised a CYP3A-humanised mouse model to comprehensively evaluate the effects of the three Kampo medicines on CYP3A activity, including an analysis of the area under the plasma concentration-time curve (AUC) and AUC ratio (AUCR).None of the three Kampo medicines tested significantly affected the AUC of the CYP3A substrate triazolam or the AUCRs of triazolam metabolites.4. These results provide important preclinical evidence indicating the lack of a significant net effect on CYP3A-mediated DDIs for Hochuekkito, Goreisan and Ninjin'yoeito under the tested repeated-dosing conditions, thereby supporting their safe and proper use.