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Aim: To develop a pharmacokinetic-pharmacodynamic (PK-PD) model to characterize and predict the bactericidal effect of nemonoxacin against Streptococcus pneumoniae in vitro.Methods: The profiles of nemonoxacin following single oral administration of 100, 250, 500 and 750mg were simulated in vitro.Four strains of S.pneumoniae with different sensitivity to penicillin were selected.A PK-PD model was developed to characterize the relationship between PK of nemonoxacin and its bactericidal effect, where the bacteria growth and death were described using Logistic model and sigmoid Emax function, respectively.Simulations were performed to investigate the impact of dosing regimen including dosage and dosing interval on the mean bactericidal rate and the PD ofnemonoxacin.Experiment was conducted to validate the simulation results.Results: The two-compartment kinetics ofnemonoxacin and its dynamic time-kill curves were well described by the PK-PD model.The maximal killing rate ofnemonoxacin (Kmax) and the growth rate of S.pneumoniae were 1.76h-1 and 0.489h-1 (MIC=0.06μg/mL), respectively.The Kmax decreased in a dependent manner when the MIC increased.When MIC below 0.25μg/mL, the daily dose of nemonoxacin inhibiting the initial growth of S.pneumoniae was less than 70rg, while the killing effect of nemonoxacin increases along with the dose.In contrast, when the MIC increased to 2μg/mL, the daily dose of nemonoxacin inhibiting the initial bacteria growth was more than 180mg, and shorter dosing interval could gain better bactericidal effect.The simulation results of PK-PD model were validated by the experiment.Conclusions: Daily administration of nemonoxacin provides rapid bactericidal effect when the MIC is low.Multiple dosing in a day can gain better killing effect when the MIC is high.This paper constitutes a basis for the future development of PK-PD model for quinolones on the S.pneumoniae in this paradigm.