title: Pharmacokinetics and pharmacodynamics of nemonoxacin against Streptococcus pneumoniae in an in vitro infection model.
abstract: 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.
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University & Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Liang
authors.forename: Yuan-cheng
authors.initials: YC
authors.lastname: Chen
authors.forename: Yu-ran
authors.initials: YR
authors.lastname: Cao
authors.forename: Xiao-fang
authors.initials: XF
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.forename: Jia-li
authors.initials: JL
authors.lastname: Hu
authors.forename: Miao
authors.initials: M
authors.lastname: Zhao
authors.forename: Qing-lan
authors.initials: QL
authors.lastname: Guo
authors.forename: Shu-jing
authors.initials: SJ
authors.lastname: Zhang
authors.forename: Xiao-jie
authors.initials: XJ
authors.lastname: Wu
authors.forename: De-mei
authors.initials: DM
authors.lastname: Zhu
authors.forename: Ying-yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015373:Bacterial Typing Techniques; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial; D008826:Microbial Sensitivity Tests; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology; D015363:Quinolones / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D015363:Quinolones; C543520:nemonoxacin