{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:00:46Z","timestamp":1788454846270,"version":"build-2803163510"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"China Medical and Health Development Foundation","award":["202427"],"award-info":[{"award-number":["202427"]}]},{"name":"Drug Safety Research Project by Adverse Drug Reactions Journal","award":["ADR2024MS21"],"award-info":[{"award-number":["ADR2024MS21"]}]},{"name":"Jiangsu Pharmaceutical Association Hospital Pharmacy Research Project","award":["A202228"],"award-info":[{"award-number":["A202228"]}]},{"name":"Jiangsu Pharmaceutical Association Hospital Pharmacy Research Project","award":["SY202304-3"],"award-info":[{"award-number":["SY202304-3"]}]},{"name":"Jiangsu Pharmaceutical Association Hospital Pharmacy Research Project","award":["H202334"],"award-info":[{"award-number":["H202334"]}]},{"name":"Jiangsu Research Hospital Association for Precision Medication","award":["JY202203"],"award-info":[{"award-number":["JY202203"]}]},{"name":"Jiangsu Research Hospital Association for Precision Medication","award":["JY202212"],"award-info":[{"award-number":["JY202212"]}]},{"name":"Gusu Talent Program","award":["GSWS2022069"],"award-info":[{"award-number":["GSWS2022069"]}]},{"name":"Gusu School of Nanjing Medical University","award":["GSKY20240207"],"award-info":[{"award-number":["GSKY20240207"]}]},{"DOI":"10.13039\/501100007289","name":"Nanjing Medical University","doi-asserted-by":"publisher","award":["2024KF0237"],"award-info":[{"award-number":["2024KF0237"]}],"id":[{"id":"10.13039\/501100007289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018556","name":"Suzhou Science and Technology Project","doi-asserted-by":"publisher","award":["SKJYD2021172"],"award-info":[{"award-number":["SKJYD2021172"]}],"id":[{"id":"10.13039\/501100018556","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Elderly patients are at an increased risk of supratherapeutic linezolid exposure, and elevated trough concentrations of linezolid and its metabolite (PNU-142300) are associated with the development of linezolid-induced thrombocytopenia. Clarifying the population pharmacokinetic (PPK) characteristics of linezolid and PNU-142300 in this population is critical for optimizing therapeutic strategies. This study aimed to develop a PPK model for linezolid and PNU-142300 in elderly patients to guide dose adjustments and mitigate thrombocytopenia risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients aged \u226565\u2005years receiving linezolid therapy were enrolled. Concentrations of linezolid and PNU-142300 were quantified using LC-MS\/MS. Covariate analysis was conducted via stepwise forward inclusion and backward elimination. Model evaluation included goodness-of-fit plots, prediction-corrected visual predictive checks, and nonparametric bootstrap validation. Monte Carlo simulations were performed to identify optimal dosing regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 149 concentrations from 114 patients were analysed. Creatinine clearance (CLCr) significantly influenced the clearance of both linezolid and PNU-142300. Population mean estimates for clearance were 2.02 L\/h (linezolid) and 1.57 L\/h (PNU-142300), with an equal volume of distribution of 31.17 L. The model demonstrated robust stability and predictive performance. For patients with CLCr of 15\u201329\u2005mL\/min, 200\u2005mg q12h achieved optimal linezolid exposure, with a 78.6% probability of maintaining PNU-142300 below the toxicity threshold. For patients with CLCr of 30\u201389\u2005mL\/min, 200\u2005mg q8h provided therapeutic exposure with &amp;gt;80% probability of avoiding metabolite toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This first PPK model of linezolid and PNU-142300 in elderly patients supports individualized dosing to reduce thrombocytopenia risk. Linezolid dose reduction may be necessary in elderly patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf329","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T11:42:06Z","timestamp":1756294926000},"page":"3001-3010","source":"Crossref","is-referenced-by-count":3,"title":["Population pharmacokinetic model of linezolid and its metabolite PNU-142300 in elderly patients"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8405-8919","authenticated-orcid":false,"given":"Xianglong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital , Suzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiJuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, 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,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Medical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital , Suzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lufen","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital , Suzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital , Suzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenjia","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of 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