CONCLUSION: The PBPK model developed via the middle-out approach provides a quantitative tool to predict CYP-mediated DDI with dasotraline as either a victim or a perpetrator and the impact of polymorphic CYP2B6 on dasotraline PK. This model may aid in optimizing dosing strategies to minimize the risks associated with CYP-mediated interactions and significant accumulation following repeated dosing.
