{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T22:02:52Z","timestamp":1757541772672,"version":"3.41.2"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["17DZ1910402 19411964900"],"award-info":[{"award-number":["17DZ1910402 19411964900"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People\u2019s Republic of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Nemonoxacin, a novel nonfluorinated quinolone for the treatment of community-acquired pneumonia. We reported the pharmacokinetic\/pharmacodynamic (PK\/PD) targets and PK\/PD breakpoints of nemonoxacin against <jats:italic>Streptococcus pneumoniae<\/jats:italic> using a neutropenic murine lung infection model. Single-dose PK analysis after subcutaneous administration of nemonoxacin at doses from 2.5 to 80\u00a0mg\/kg showed maximum plasma concentration (C<jats:sub>max<\/jats:sub>) 0.56\u20137.32\u00a0mg\/L, area under the concentration-time curve from 0 to 24\u00a0h (AUC<jats:sub>0-24<\/jats:sub>) 0.67\u201326.10\u00a0mg\u00b7h\/L, and elimination half-life (T<jats:sub>1\/2<\/jats:sub>) 0.8\u20131.4\u00a0h. The epithelial lining fluid (ELF) penetration ratio of total drug was 1.40. Dose fractionation (1.25\u201380\u00a0mg\/kg\/day, every 24, 12, 8, and 6\u00a0h) and dose escalation studies (1.25\u2013160\u00a0mg\/kg, every 24\u00a0h) were conducted. The sigmoid E<jats:sub>max<\/jats:sub> Hill equation was used to describe the dose-response data. The free-drug plasma <jats:italic>f<\/jats:italic>AUC<jats:sub>0-24<\/jats:sub>\/MIC ratio was considered the PK\/PD index most closely associated with efficacy (R<jats:sup>2<\/jats:sup> 0.9268). Median <jats:italic>f<\/jats:italic>AUC<jats:sub>0-24<\/jats:sub>\/MIC associated with static, 1-log<jats:sub>10<\/jats:sub> and 2-log<jats:sub>10<\/jats:sub>\u00a0CFU reduction from baseline were 8.6, 23.2 and 44.4, respectively. Monte Carlo simulation showed 500\u00a0mg qd and 750\u00a0mg qd oral doses of nemonoxacin were able to achieve 90% probability of target attainment (PTA) against bacteria with MIC of 0.5\u00a0mg\/L and 1\u00a0mg\/L. We recommended susceptibility (S) \u2264 0.5\u00a0mg\/L, intermediate (I) = 1\u00a0mg\/L and resistant (R) \u2265 2\u00a0mg\/L as the PK\/PD breakpoints for nemonoxacin against <jats:italic>S. pneumoniae<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fphar.2021.658558","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T07:02:52Z","timestamp":1620111772000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacokinetics and Pharmacodynamics of Nemonoxacin in a Neutropenic Murine Lung Infection Model Against Streptococcus Pneumoniae"],"prefix":"10.3389","volume":"12","author":[{"given":"Xin","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuancheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaxin","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingchen","family":"Bian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiqing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beining","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4915","DOI":"10.1128\/AAC.00078-09","article-title":"In vitro activity of Nemonoxacin, a Novel Nonfluorinated Quinolone, against 2,440 Clinical Isolates","volume":"53","author":"Adam","year":"2009","journal-title":"Aac"},{"key":"B2","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/S0891-5520(03)00061-8","article-title":"Clinical Pharmacodynamics of Quinolones","volume":"17","author":"Ambrose","year":"2003","journal-title":"Infect. 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