Aim:Rivaroxaban (Bayer Healthcare AG, Wuppertal, Germany), an oral, direct factor Xa (FXa) inhibitor for the prevention and treatment of thromboembolic disorders has been approved for nonvalvular atrial fibrillation and prophylaxis of DVT.The objective of this research was to investigate the age and food effect on pharmacokinetics and pharmacodynamics of rivaroxaban in healthy Chinese volunteers and improve the utilization of rivaroxaban in clinical practice.Method:Two clinical trials were performed in healthy Chinese adult and elderly volunteers separately1,2.A sequential population PK/PD analysis was performed using plasma concentration, Xa activity, aPTT, PT and Hep from both clinical trials through Phoenix NLME (Ver.1.2).Results:A two compartment pharmacokinetic model with first-order absorption and elimination best describe the rivaroxaban plasma concentration data.A dose-dependent bioavailability in fasted status was identified and the corresponding relative bioavailability to fed status was modeled and estimated.The estimated FD50 was 24mg, indicating a 60% to 70% bioavailability decrease in the 10mg to 20mg labeled dose when administered without food.Indirect response model was selected to describe the pharmacodynamic profile of factor Xa activity, aPTT, PT and heparin.Gender difference in both PK and PD between two age groups were identified and estimated.The model was evaluated by visual predictive check and bootstrap, no major model misspecification was observed.Conclusion:A sequential population PK/PD model was developed and reasonable parameters were obtained from the data from two clinical trials in healthy Chinese subjects, demonstrating predictable pharmacokinetics and pharmacodynamics profile