Background and Objective: Afloqualone (AFQ) is a quinazoline family GABAergic drug used as muscle relaxant. After oral administration of AFQ, greatly elevated exposure in some individuals were observed which might cause severe side effects. The aim of this study was to develop a population pharmacokinetic model of AFQ and search possible reason of high inter-individual variability (IIV) in the clinical study and further demonstrate its impact on exposure on AFQ through simulation. Methodology: To evaluate the exposure of AFQ and confirm the high difference between subjects, non-compartmental analysis was assessed. A Population PK model of AFQ was developed using healthy human AFQ PK data and simulation study was performed with final PK model. Results: A two-compartment model with first order absorption and elimination was used to explain the pharmacokinetics of AFQ. The high level of HIV in AFQ exposure was explained through assumption two subject group with high exposure group (HEG) or normal exposure group (NEG). Through simulations, it was proved that big difference of AFQ exposure between subjects could be observed in some individual and dose of AFQ needs to be reduced for such subjects in HEG. Conclusion: Population PK model of AFQ for explaining high IIV was successfully developed and exposure of AFQ between subjects was simulated. Finally, suggesting an appropriate dose of AFQ in HEG which could be had possibility of genetic polymorphism.