{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T19:20:43Z","timestamp":1786476043342,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Linezolid is a widely used antimicrobial agent in clinical practice; however, its usage is often limited by linezolid\u2010induced thrombocytopenia (LIT). While prior studies have assessed linezolid plasma concentrations, the clinical relevance of its metabolites, PNU\u2010142300 and PNU\u2010142586, remains unclear. This study aimed to investigate the association between these metabolite concentrations and LIT, and to identify predictive thresholds. This study retrospectively analyzed patients treated with linezolid at Osaka Metropolitan University Hospital between January 2017 and December 2024. Patient characteristics, trough concentrations (C\n                    <jats:sub>trough<\/jats:sub>\n                    ), AUC\n                    <jats:sub>24<\/jats:sub>\n                    , and pharmacokinetic parameters of linezolid and its metabolites were compared among patients with and without thrombocytopenia. Receiver operating characteristic (ROC) analysis identified thresholds for LIT prediction. Risk factors were assessed using multivariate logistic regression analysis. Forty\u2010eight patients were included, with thrombocytopenia developing in 26 patients (54.2%). C\n                    <jats:sub>trough<\/jats:sub>\n                    and AUC\n                    <jats:sub>24<\/jats:sub>\n                    of PNU\u2010142300 and PNU\u2010142586 were significantly higher in the thrombocytopenia group; meanwhile, linezolid C\n                    <jats:sub>trough<\/jats:sub>\n                    and AUC\n                    <jats:sub>24<\/jats:sub>\n                    did not differ significantly. ROC analysis identified C\n                    <jats:sub>trough<\/jats:sub>\n                    \u22651.43 \u00b5g\/mL and AUC\n                    <jats:sub>24<\/jats:sub>\n                    \u226537.8 mg h\/L for PNU\u2010142586 as predictive thresholds. Multivariate analysis revealed that linezolid therapy \u226514 days (OR = 9.53,\n                    <jats:italic>P<\/jats:italic>\n                    = \u00a0.044) and PNU\u2010142586 C\n                    <jats:sub>trough<\/jats:sub>\n                    \u22651.43 \u00b5g\/mL (OR = 37.60,\n                    <jats:italic>P<\/jats:italic>\n                    = \u00a0.002) as independent risk factors. Elevated PNU\u2010142586 concentrations were associated with a higher cumulative incidence of LIT. Accumulation of linezolid metabolites, especially PNU\u2010142586, is closely associated with LIT. Monitoring of PNU\u2010142586 may improve the safety of linezolid therapy and support individualized dosing strategies.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70124","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T05:36:51Z","timestamp":1763012211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluating the Impact of Linezolid Metabolites: PNU\u2010142300 and PNU\u2010142586 on the Development of Linezolid\u2010Induced Thrombocytopenia in Adult Patients"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8625-3345","authenticated-orcid":false,"given":"Norihiro","family":"Sakurai","sequence":"first","affiliation":[{"name":"Department of Infection Control Science Osaka Metropolitan University Graduate School of Medicine  Abeno\u2010ku Osaka Japan"},{"name":"Department of Pharmacy Osaka Metropolitan University Hospital  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Abeno\u2010ku Osaka Japan"},{"name":"Department of Infection Control Osaka Metropolitan University Hospital  Abeno\u2010ku Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Infection Control Science Osaka Metropolitan University Graduate School of Medicine  Abeno\u2010ku Osaka Japan"},{"name":"Department of Pharmacy Tazuke Kofukai Medical Research Institute Kitano Hospital  Kita\u2010ku Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waki","family":"Imoto","sequence":"additional","affiliation":[{"name":"Department of Infection Control Science Osaka Metropolitan University Graduate School of Medicine  Abeno\u2010ku Osaka Japan"},{"name":"Department of Infection Control Osaka Metropolitan University Hospital  Abeno\u2010ku Osaka Japan"},{"name":"Research Center for Infectious Disease Sciences (RCIDS) Osaka Metropolitan University Graduate School of Medicine  Abeno\u2010ku Osaka Japan"},{"name":"Osaka International Research Center for Infectious Diseases (OIRCID) Osaka Metropolitan University  Abeno\u2010ku Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Infection Control Science Osaka Metropolitan University Graduate School of Medicine  Abeno\u2010ku Osaka Japan"},{"name":"Department of Infection Control Osaka Metropolitan University Hospital  Abeno\u2010ku Osaka Japan"},{"name":"Research Center for Infectious Disease Sciences (RCIDS) Osaka Metropolitan University Graduate School of Medicine  Abeno\u2010ku Osaka Japan"},{"name":"Osaka International Research Center for Infectious Diseases (OIRCID) Osaka Metropolitan University  Abeno\u2010ku Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasutaka","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department 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