{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:16:07Z","timestamp":1788142567057,"version":"build-2803163510"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100006471","name":"College of Veterinary Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006471","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012601","name":"South China Agricultural University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012601","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterize pulmonary pharmacokinetics (PK), epithelial lining fluid (ELF) exposure, antibacterial activity and preliminary PK\/pharmacodynamic (PK\/PD) relationships of the pleuromutilin derivative APTM in neutropenic murine lung infection models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma PK and ELF exposure were assessed after a single oral dose in healthy mice. Minimum inhibitory concentrations (MICs) and in vitro time-kill activity were determined against methicillin-resistant Staphylococcus aureus USA300 and Streptococcus pneumoniae ATCC 49619. In vivo efficacy was assessed in neutropenic murine lung infection models. The ratio of the 24\u2005h area under the plasma concentration\u2013time curve to MIC (AUC0\u201324h\/MIC) and the ratio of maximum plasma concentration to MIC (Cmax\/MIC) were evaluated as candidate indices using Sigmoid Imax models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Plasma exposure increased approximately linearly over 10\u2013150\u2005mg\/kg. Mean total ELF\/plasma ratios were 1.21 for Cmax and 2.05 for the area under the concentration\u2013time curve from time zero to infinity (AUC0\u2013\u221e). MICs were 0.25\u2005mg\/L for USA300 and 0.5\u2005mg\/L for ATCC 49619. Relative to the 2\u2005h baseline, maximal mean reductions in pulmonary bacterial burden at 150\u2005mg\/kg were 3.39 log10\u2005cfu\/mL for USA300 and 1.63 log10\u2005cfu\/mL for ATCC 49619. Under the single every-12-h (q12h) regimen, AUC0\u201324h\/MIC showed a stronger association with antibacterial efficacy than Cmax\/MIC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>APTM achieved measurable pulmonary exposure and antibacterial activity in murine lung infection models. AUC0\u201324h\/MIC was the best-performing exposure metric among those evaluated under the present conditions; it should not be interpreted as a definitive PK\/PD driver. These exploratory, isolate-specific findings support further PK\/PD studies of APTM for respiratory infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag306","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:44:40Z","timestamp":1787312680000},"source":"Crossref","is-referenced-by-count":0,"title":["Pulmonary pharmacokinetics, epithelial lining fluid exposure and PK\/PD characterization of the novel pleuromutilin derivative APTM against methicillin-resistant\n                    <i>Staphylococcus aureus<\/i>\n                    and\n                    <i>Streptococcus pneumoniae<\/i>\n                    in mice"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8610-6184","authenticated-orcid":false,"given":"Weicong","family":"Yang","sequence":"first","affiliation":[{"name":"National Veterinary Drug Residue Standard Laboratory, College of Veterinary Medicine, South China Agricultural University , Guangzhou ,","place":["China"]},{"name":"National Veterinary Drug Safety Evaluation (Environmental Assessment) Laboratory, College of Veterinary Medicine, South China Agricultural University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luoju","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Qilu-Kingphar Pharmaceutical Co., Ltd. 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