{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:44:02Z","timestamp":1792590242602,"version":"4.5.0"},"reference-count":34,"publisher":"American Chemical Society (ACS)","issue":"41","license":[{"start":{"date-parts":[[2027,10,10]],"date-time":"2027-10-10T00:00:00Z","timestamp":1823126400000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mycoplasma gallisepticum is a major causative agent of chronic respiratory disease in poultry, and effective antimicrobial therapy remains essential for disease control. In this study, the antimycoplasmal activity, pharmacokinetics, therapeutic efficacy, and pharmacokinetic\/pharmacodynamic (PK\/PD) model of Pleuro2\u20134, a novel pleuromutilin candidate, were systematically evaluated against M. gallisepticum. Pleuro2\u20134 exhibited potent in vitro activity (MIC = 0.0078 \u03bcg\/mL) and concentration-dependent killing. Following oral administration in chicks, Pleuro2\u20134 was rapidly converted to its active metabolite and displayed rapid absorption and sustained exposure in lung tissue. In an M. gallisepticum infection model, Pleuro2\u20134 alleviated respiratory lesions, reduced mycoplasmal loads, and suppressed inflammatory responses. PK\/PD integration using an inhibitory sigmoid Emax model identified AUC0\u201324h\/MIC as the PK\/PD index for dose optimization. The bactericidal target was 3372.82 h, corresponding to a recommended oral dosage of 44.99 mg\/kg once daily for three consecutive days. These findings support Pleuro2\u20134 as a promising candidate for avian mycoplasmosis treatment.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c08587","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T05:02:07Z","timestamp":1791608527000},"page":"32357-32367","source":"Crossref","is-referenced-by-count":0,"title":["PK\/PD Modeling\nof a Novel Pleuromutilin Derivative\nPleuro2\u20134 against\n                    <i>Mycoplasma gallisepticum<\/i>\n                    in Chicks"],"prefix":"10.1021","volume":"74","author":[{"given":"Feifei","family":"Zhao","sequence":"first","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhen","family":"Zhu","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghao","family":"Huang","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2006-5755","authenticated-orcid":true,"given":"Dongping","family":"Zeng","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenguang","family":"Xiong","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2293-0287","authenticated-orcid":true,"given":"Youzhi","family":"Tang","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1103-7170","authenticated-orcid":true,"given":"Zhenling","family":"Zeng","sequence":"additional","affiliation":[{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]},{"name":"South China Agricultural University , , ,","place":["Guangzhou, China, 510642"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"2026102109084595200_cit1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.2147\/VMRR.S360669","article-title":"Seroprevalence\nand Associated Risk Factors of Mycoplasma gallisepticum Infection in Poultry Farms of Hawasa and Bishoftu, Central Ethiopia","volume":"13","author":"Shiferaw","year":"2022","journal-title":"Vet. 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Sci."},{"key":"2026102109084595200_cit4","doi-asserted-by":"publisher","first-page":"75","DOI":"10.3389\/fvets.2016.00075","article-title":"Pharmacokinetic\/Pharmacodynamic Profiles of Tiamulin in an Experimental\nIntratracheal Infection Model of Mycoplasma gallisepticum","volume":"3","author":"Xiao","year":"2016","journal-title":"Front. Vet. Sci."},{"key":"2026102109084595200_cit5","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1128\/AAC.50.4.1458-1462.2006","article-title":"Interaction of pleuromutilin\nderivatives with the ribosomal peptidyl transferase center","volume":"50","author":"Long","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026102109084595200_cit6","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1021\/acs.jafc.6b04377","article-title":"Comprehensive\nAnalysis of Tiamulin Metabolites in Various\nSpecies of Farm Animals Using Ultra-High-Performance Liquid Chromatography\nCoupled to Quadrupole\/Time-of-Flight","volume":"65","author":"Sun","year":"2017","journal-title":"J. Agric.\nFood Chem."},{"key":"2026102109084595200_cit7","doi-asserted-by":"publisher","first-page":"3754","DOI":"10.1128\/AAC.00200-15","article-title":"In vivo pharmacokinetic\/pharmacodynamic\nprofiles of valnemulin in an experimental intratracheal Mycoplasma gallisepticum infection model","volume":"59","author":"Xiao","year":"2015","journal-title":"Antimicrob.\nAgents Chemother."},{"key":"2026102109084595200_cit8","doi-asserted-by":"publisher","first-page":"9201","DOI":"10.1021\/jf5012402","article-title":"In vitro and\nin vivo metabolite profiling of valnemulin using ultraperformance\nliquid chromatography-quadrupole\/time-of-flight hybrid mass spectrometry","volume":"62","author":"Yang","year":"2014","journal-title":"J. Agric. 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Pharmacol."},{"key":"2026102109084595200_cit17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169134","article-title":"Determination\nof the\nMutant Selection Window and Evaluation of the Killing of Mycoplasma gallisepticum by Danofloxacin, Doxycycline, Tilmicosin, Tylvalosin\nand Valnemulin","volume":"12","author":"Zhang","year":"2017","journal-title":"PLoS One"},{"key":"2026102109084595200_cit18","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.femsle.2005.05.012","article-title":"Induction of macrolide\nresistance in Mycoplasma gallisepticum in vitro and its resistance -related mutations\nwithin domain V of 23S rRNA","volume":"247","author":"Wu","year":"2005","journal-title":"FEMS Microbiol\nLett."},{"key":"2026102109084595200_cit19","doi-asserted-by":"publisher","first-page":"926","DOI":"10.3389\/fmicb.2017.00926","article-title":"The PK - PD Relationship\nand Resistance Development of Danofloxacin against Mycoplasma gallisepticum in An In Vivo Infection Model","volume":"8","author":"Zhang","year":"2017","journal-title":"Front. Microbiol."},{"key":"2026102109084595200_cit20","doi-asserted-by":"publisher","first-page":"1802515","DOI":"10.3389\/fimmu.2026.1802515","article-title":"Effects of immunosuppression\non tracheal\nmucosal responses after infection with Mycoplasma gallisepticum in vaccinated and unvaccinated chickens","volume":"17","author":"Arachchige","year":"2026","journal-title":"Front.\nImmunol."},{"key":"2026102109084595200_cit21","doi-asserted-by":"publisher","first-page":"109182","DOI":"10.1016\/j.vetmic.2021.109182","article-title":"Effects\nof immunosuppression on the efficacy of vaccination against Mycoplasma gallisepticum infection in chickens","volume":"260","author":"Arachchige","year":"2021","journal-title":"Vet. Microbiol."},{"key":"2026102109084595200_cit22","doi-asserted-by":"publisher","first-page":"a027110","DOI":"10.1101\/cshperspect.a027110","article-title":"Pleuromutilins: Potent\nDrugs for Resistant Bugs-Mode of Action and\nResistance","volume":"7","author":"Paukner","year":"2017","journal-title":"Cold Spring Harbor Perspect. Med."},{"key":"2026102109084595200_cit23","doi-asserted-by":"publisher","first-page":"501","DOI":"10.3390\/cells8050501","article-title":"gga-miR-146c\nActivates TLR6\/MyD88\/NF-\u03baB Pathway through Targeting MMP16 to\nPrevent Mycoplasma gallisepticum (HS Strain) Infection\nin Chickens","volume":"8","author":"Zhang","year":"2019","journal-title":"Cells"},{"key":"2026102109084595200_cit24","doi-asserted-by":"publisher","first-page":"4410","DOI":"10.1021\/ja500367u","article-title":"Tuning the biological activity profile of antibacterial\npolymers via subunit substitution pattern","volume":"136","author":"Liu","year":"2014","journal-title":"J.\nAm. Chem. Soc."},{"key":"2026102109084595200_cit25","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1093\/jac\/dkg269","article-title":"The mutant\nselection window and antimicrobial resistance","volume":"52","author":"Drlica","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"2026102109084595200_cit26","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1111\/j.1749-6632.2011.06219.x","article-title":"Are pleuromutilin\nantibiotics finally fit for human use?","volume":"1241","author":"Novak","year":"2011","journal-title":"Ann.\nN.Y. Acad. Sci."},{"key":"2026102109084595200_cit27","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.phrs.2017.11.010","article-title":"Antibacterial\nactivity and pharmacokinetic profile of a promising antibacterial\nagent: 14-O-[(4-Amino-6-hydroxy-pyrimidine-2-yl)thioacetyl] mutilin","volume":"129","author":"Shang","year":"2018","journal-title":"Pharmacol. Res."},{"key":"2026102109084595200_cit28","doi-asserted-by":"publisher","first-page":"iii5","DOI":"10.1093\/jac\/dkz085","article-title":"In vivo pharmacodynamics\nof lefamulin,\nthe first systemic pleuromutilin for human use, in a neutropenic murine\nthigh infection model","volume":"74","author":"Wicha","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"2026102109084595200_cit29","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1093\/chromsci\/bmy033","article-title":"Determination\nof a New Pleuromutilin Derivative in Broiler Chicken Plasma by RP-HPLC-UV\nand Its Application to a Pharmacokinetic Study","volume":"56","author":"Shang","year":"2018","journal-title":"J. Chromatogr. Sci."},{"key":"2026102109084595200_cit30","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1016\/j.vaccine.2005.09.045","article-title":"Age related differences\nin the immune response to vaccination and infection with Mycoplasma gallisepticum","volume":"24","author":"Gaunson","year":"2006","journal-title":"Vaccine"},{"key":"2026102109084595200_cit31","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1080\/03079450500179954","article-title":"Real-time polymerase\nchain reaction for the qualitative\nand quantitative detection of Mycoplasma gallisepticum","volume":"34","author":"Mekkes","year":"2005","journal-title":"Avian. Pathol."},{"key":"2026102109084595200_cit32","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s40262-019-00813-w","article-title":"Pharmacokinetics and Target Attainment\nof Antibiotics in Critically Ill Children: A Systematic Review of\nCurrent Literature","volume":"59","author":"Hartman","year":"2020","journal-title":"Clin. Pharmacokinet."},{"key":"2026102109084595200_cit33","doi-asserted-by":"publisher","first-page":"104255","DOI":"10.1016\/j.micpath.2020.104255","article-title":"Pharmacokinetic-pharmacodynamic\nintegration and resistance of tiamulin\nagainst Mycoplasma hyopneumoniae in an in vitro dynamic\nmodel","volume":"147","author":"Huang","year":"2020","journal-title":"Microb. Pathog."},{"key":"2026102109084595200_cit34","doi-asserted-by":"publisher","first-page":"403","DOI":"10.3390\/antibiotics11030403","article-title":"Rational Use of Danofloxacin for Treatment\nof Mycoplasma gallisepticum in Chickens Based on\nthe Clinical\nBreakpoint and Lung Microbiota Shift","volume":"11","author":"Wang","year":"2022","journal-title":"Antibiotics-Basel"}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c08587","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/41\/32357\/68810174\/acs.jafc.6c08587.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/41\/32357\/68810174\/acs.jafc.6c08587.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:09:33Z","timestamp":1792588173000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/41\/32357\/5448453\/PK-PD-Modeling-of-a-Novel-Pleuromutilin-Derivative"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,10]]},"references-count":34,"journal-issue":{"issue":"41","published-online":{"date-parts":[[2026,10,10]]},"published-print":{"date-parts":[[2026,10,21]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c08587","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,10]]}}}