{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:44:41Z","timestamp":1788291881901,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Chemotherapy\u2010induced peripheral neuropathy (CIPN) is a common neurological toxicity of paclitaxel treatment in patients with cancer that can cause irreversible reductions in function and quality of life. CIPN risk is higher in patients with greater systemic paclitaxel exposure, including the maximum concentration at the end of infusion (C\n                    <jats:sub>max<\/jats:sub>\n                    ). The objective of this study is to build a paclitaxel pharmacokinetic\u2010pharmacodynamic (PK\u2010PD) model of CIPN that could inform personalized dosing strategies. Data was obtained from the UMCC2014.002 clinical study of patients with breast cancer receiving weekly 1\u2010h infusion of 80\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    paclitaxel for 12\u2009weeks. The PK model, built using paclitaxel C\n                    <jats:sub>max<\/jats:sub>\n                    and 16\u201324\u2009h samples was combined with weekly a CIPN20 questionnaire to build the model. Model performance was explored by simulating CIPN resulting from a standard (80\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    \u2009\u00d7\u200912 weekly doses) and enhanced (100\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    \u2009\u00d7\u20096\u2009+\u200980\u2009mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    \u2009\u00d7\u20096) dosing regimen and compared with the actual CIPN from patients receiving these regimens within the CALGB C9840 clinical trial. A two\u2010compartment PK model and a turnover PD model incorporating an effect compartment and threshold structure best described the data. The PK\u2010PD model adequately captures CIPN from patients in UMCC2014.002. Simulations recapitulate CIPN from standard (18% simulated vs. 21% actual) and enhanced (35% simulated vs. 30% actual) paclitaxel regimens from CALGB C9840. A novel PK\u2010PD model adequately describes CIPN from weekly paclitaxel. This CIPN PK\u2010PD model may be able to inform personalized dosing strategies that reduce CIPN and improve treatment outcomes in paclitaxel\u2010treated patients.\n                  <\/jats:p>","DOI":"10.1111\/cts.70404","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T14:29:18Z","timestamp":1763130558000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetic\u2010Pharmacodynamic Model of Paclitaxel\u2010Induced Peripheral Neuropathy"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9936-0476","authenticated-orcid":false,"given":"Yuchen","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy University of Michigan College of Pharmacy  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-5034","authenticated-orcid":false,"given":"Manjunath P.","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University of Michigan College of Pharmacy  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4771-5930","authenticated-orcid":false,"given":"N. Lynn","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology\/Oncology University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0501-1035","authenticated-orcid":false,"given":"Daniel L.","family":"Hertz","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy University of Michigan College of Pharmacy  Ann Arbor Michigan 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