【Purpose】Drug interactions (DIs) occur through interactions on transporters and metabolic enzymes in the co-administration of multiple drugs, suggesting the importance of accurate prediction of DIs for the risk management of concomitant medications. Nonetheless, there is currently a lack of methods for predicting DIs mediated by intestinal transporters (e.g. P-glycoprotein (P-gp)) and metabolic enzymes (e.g. cytochrome P450s (CYPs)). Therefore, it is necessary to propose a prediction model for DIs mediated by intestinal transporters and CYPs. We have previously reported the static prediction method for multiple CYPs-mediated DIs integrating in vitro and in vivo information1). In this study, we proposed the static DIs prediction model considering intestinal P-gp and multiple CYPs to expand the reported model.【Method】Information on in vitro studies, DIs mediated by P-gp and CYPs, and pharmacokinetics were collected from multiple literature. Additionally, we developed the in vitro and in vivo absorption models to estimate the contribution ratio (CR) of intestinal P-gp and CYP3A from in vitro permeability and metabolic clearance. CRs and inhibition ratios (IRs) for P-gp and CYPs were estimated using the Markov Chain Monte Carlo method, and the predictability was evaluated by comparison between the predicted and observed values of the area under the concentration-time curve ratio (AUCR) and elimination half-life ratio (t_1/2R).【Results】The predicted values of AUCR and t_1/2R were correlated with the observed ones using the estimated CRs and IRs. 【Conclusion】The static model integrating P-gp and CYPs can predict DIs in the small intestine and liver among comprehensive substrates and inhibitors. Application of the model can contribute to the management of intestinal and hepatic DIs.【Reference】1)Hozuki et al., Clin Pharmacokinet. 62(6) 849-860, 2023