{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:05:26Z","timestamp":1784203526594,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intravenous polymyxin B (PMB) is widely used for treating drug\u2010resistant gram\u2010negative pneumonia, though its efficacy in pulmonary infections is considered limited. This study aims to identify patients with severe pulmonary infections suitable for treatment with intravenous PMB alone and to recommend individualized optimal dosing regimens. Physiologically based pharmacokinetic (PBPK) models, developed using data from mice, healthy subjects, and critically ill patients, were employed to predict PMB concentrations in epithelial lining fluid (ELF) and plasma. All models were validated against published pharmacokinetic data, and Monte Carlo simulations were used to evaluate various dosing regimens. The therapeutic target was defined as an ELF steady\u2010state 24 h area under the concentration\u2010time curve to minimum inhibitory concentration (AUC\n                    <jats:sub>ss,24h<\/jats:sub>\n                    \/MIC) \u2265\u200950. Simulations showed that intravenous PMB maintenance regimens of 100\u2009mg, 1.25\u2009mg\/kg, or 1.50\u2009mg\/kg q12h enabled 94.4%, 82.2%, and 93.5% of critically ill patients to achieve the ELF pharmacokinetic\/pharmacodynamic (PK\/PD) target for pathogens with an MIC of 1\u2009mg\/L. A plasma AUC\n                    <jats:sub>ss,24h<\/jats:sub>\n                    \/MIC threshold of 80.6 was identified as an alternative PK\/PD target, with retrospective analysis confirming significantly better outcomes for patients exceeding this threshold (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.038), warranting prospective validation. Overall, PBPK modeling supports 100\u2009mg or 1.50\u2009mg\/kg q12h as candidate initial intravenous regimens for critically ill patients with pulmonary infections. Dosing adjustments based on MIC and plasma AUC\n                    <jats:sub>ss,24h<\/jats:sub>\n                    \/MIC value are recommended. Adjunctive nebulization or combination therapy is advised for MICs \u2265\u20092\u2009mg\/L, while 50\u2009mg q12h is sufficient for MICs \u2264\u20090.5\u2009mg\/L. Plasma AUC\n                    <jats:sub>ss,24h<\/jats:sub>\n                    \/MIC values exceeding 80.6 may guide individualized dosing when therapeutic drug monitoring is available.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70289","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T03:49:36Z","timestamp":1781927376000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polymyxin B Intravenous Administration Strategy Guided by Minimum Inhibitory Concentration in Critically Ill Patients With Pulmonary Infection: Insights From\n                    <scp>PBPK<\/scp>\n                    Modeling"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4837-1969","authenticated-orcid":false,"given":"Shengnan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacy The Third Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4840-1072","authenticated-orcid":false,"given":"Nan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Third Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruwei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Third Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfang","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Third Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Third Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuifang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Third Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueliang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Third Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Intensive Medicine The Third Xiangya Hospital of Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respirology &amp; 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