{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:33:44Z","timestamp":1791524024197,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Imatinib is a targeted cancer therapy that has significantly improved the care of patients with chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). However, it has been shown that the recommended dosages of imatinib are associated with trough plasma concentration (Cmin) lower than the target value in many patients. The aims of this study were to design a novel model-based dosing approach for imatinib and to compare the performance of this method with that of other dosing methods. Three target interval dosing (TID) methods were developed based on a previously published PK model to optimize the achievement of a target Cmin interval or minimize underexposure. We compared the performance of those methods to that of traditional model-based target concentration dosing (TCD) as well as fixed-dose regimen using simulated patients (n = 800) as well as real patients\u2019 data (n = 85). Both TID and TCD model-based approaches were effective with about 65% of Cmin achieving the target imatinib Cmin interval of 1000\u20132000 ng\/mL in 800 simulated patients and more than 75% using real data. The TID approach could also minimize underexposure. The standard 400 mg\/24 h dosage of imatinib was associated with only 29% and 16.5% of target attainment in simulated and real conditions, respectively. Some other fixed-dose regimens performed better but could not minimize over- or underexposure. Model-based, goal-oriented methods can improve initial dosing of imatinib. Combined with subsequent TDM, these approaches are a rational basis for precision dosing of imatinib and other drugs with exposure\u2013response relationships in oncology.<\/jats:p>","DOI":"10.3390\/pharmaceutics15041081","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T02:11:40Z","timestamp":1679969500000},"page":"1081","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["From Personalized to Precision Medicine in Oncology: A Model-Based Dosing Approach to Optimize Achievement of Imatinib Target Exposure"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-2932","authenticated-orcid":false,"given":"Sylvain","family":"Goutelle","sequence":"first","affiliation":[{"name":"Service de Pharmacie, GH Nord, Hospices Civils de Lyon, 69002 Lyon, France"},{"name":"Univ. Lyon, Universit\u00e9 Claude Bernard Lyon 1, UMR CNRS 5558, LBBE\u2014Laboratoire de Biom\u00e9trie et Biologie \u00c9volutive, 69100 Villeurbanne, France"},{"name":"Univ. Lyon, Universit\u00e9 Claude Bernard Lyon 1, ISPB\u2014Facult\u00e9 de Pharmacie de Lyon, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monia","family":"Guidi","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"},{"name":"Center for Research and Innovation in Clinical Pharmaceutical Sciences, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva and University of Lausanne, 1211 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Gotta","sequence":"additional","affiliation":[{"name":"Pediatric Pharmacology and Pharmacometrics, University of Basel Children\u2019s Hospital, 4056 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0660-082X","authenticated-orcid":false,"given":"Chantal","family":"Csajka","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Clinical Pharmaceutical Sciences, University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva and University of Lausanne, 1211 Geneva, Switzerland"},{"name":"School of Pharmaceutical Sciences, University of Geneva, 1205 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0639-5536","authenticated-orcid":false,"given":"Thierry","family":"Buclin","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7392-2418","authenticated-orcid":false,"given":"Nicolas","family":"Widmer","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva and University of Lausanne, 1211 Geneva, Switzerland"},{"name":"Pharmacy of the Eastern Vaud Hospitals, 1847 Rennaz, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrd839","article-title":"Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug","volume":"1","author":"Capdeville","year":"2002","journal-title":"Nat. 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