The aim of this paper was to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of
nemonoxacin, a novel nonfluorinated
quinolone, against Streptococcus pneumoniae in vitro. A modified
infection model was used to simulate the pharmacokinetics of
nemonoxacin following scaling of single oral doses and multiple oral dosing. Four S. pneumoniae strains with different
penicillin sensitivities were selected, and the
drug efficacy was quantified by the change in log colony counts within 24 h. A sigmoid maximum-effect (Emax) model was used to analyze the relationship between PK/PD parameters and
drug effect. Analysis indicated that the killing pattern of
nemonoxacin shows a dualism which is mainly concentration dependent when the MIC is low and that the better PK/PD index should be the area under the concentration-time curve for the free, unbound fraction of the
drug divided by the MIC (fAUC0-24/MIC), which means that giving the total daily amount of
drug as one dose is appropriate under those conditions. When the MIC is high, the time (T) dependency is important and the valid PK/PD index should be the cumulative percentage of a 24-h period in which the
drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (f%T>MIC), which means that to split the maximum daily dose into several separate doses will benefit the eradication of the bacteria. To obtain a 3-log10-unit decrease, the target values of fAUC0-24/MIC and f%T>MIC are 47.05 and 53.4%, respectively.