Aim:Todevelop and validate a general physiologicallybased pharmacokinetic (PBPK) model for hepatic pathway in Chinese adults at various ages, and to evaluate it with midazolam (substrate of CYP3A4) as a model drug.Method:Midazolam PBPK model in Chinese population at various ages was developed with SimCYP platform, and demographic and physiological data of Chinese from literatures were incorporated into the model.Pharmacokinetic (PK) data for model validation and qualification was obtained from an open-label, singledose PK and PD study of midazolam in Chinese subjects aging from 18 to >75 years old.The model was evaluated by comparing the simulated with observed PK data.In addition, the effect of age on midazolam PK in Chinese at various ages was investigated using population PK analysis and a PKPD link model was applied to evaluate the relationship between properties of PK and PD.Results:The predicted concentration-time profiles and PK parameters (e.g., CL) ofmidazolam in Chinese population were comparable to the observed.In addition, a PKPD link model was established and the age effect on the PK and PD of midazolam in Chinese adults was clarified.Conclusion:A general PBPK modelfor the prediction of drug disposition through hepatic pathway (CYP 3A4) in Chinese adults over awide age range (18 to >75 years) is presented.In the future the model can also be.applied to assess the ethnic sensitivity between Chinese and other populations (e.g.Caucasian).