{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:58:31Z","timestamp":1790621911646,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100018732","name":"Vissing Fonden","doi-asserted-by":"publisher","award":["519140"],"award-info":[{"award-number":["519140"]}],"id":[{"id":"10.13039\/100018732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010733","name":"B\u00f8rnecancerfonden","doi-asserted-by":"publisher","award":["2021\u20107410"],"award-info":[{"award-number":["2021\u20107410"]}],"id":[{"id":"10.13039\/100010733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010733","name":"B\u00f8rnecancerfonden","doi-asserted-by":"publisher","award":["2022\u20108178"],"award-info":[{"award-number":["2022\u20108178"]}],"id":[{"id":"10.13039\/100010733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010733","name":"B\u00f8rnecancerfonden","doi-asserted-by":"publisher","award":["2024\u2010001275"],"award-info":[{"award-number":["2024\u2010001275"]}],"id":[{"id":"10.13039\/100010733","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Imatinib pharmacokinetics exhibit large interindividual variability because of differences in CYP3A4 activity\u2014the main imatinib\u2010metabolizing enzyme. While therapeutic drug monitoring is effective, it requires steady\u2010state conditions and frequent sampling. The endogenous biomarker 4\u03b2\u2010hydroxycholesterol (4\u2010\u03b2\u2010OHC) has been proposed to reflect CYP3A4 activity, enabling proactive dose optimization. This study investigated 4\u2010\u03b2\u2010OHC as a CYP3A4 biomarker in leukaemia patients and its relationship with imatinib pharmacokinetics<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A pharmacokinetic study included 19 patients with chronic myeloid leukaemia or acute lymphoblastic leukaemia receiving imatinib. Blood samples were collected over 24\u2009h. Imatinib, N\u2010desmethyl imatinib, 4\u2010\u03b2\u2010OHC and 4\u03b1\u2010hydroxycholesterol (4\u2010\u03b1\u2010OHC) plasma concentrations were quantified by liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS), while total cholesterol was measured by clinical chemistry autoanalyser. CYP3A4 activity was estimated using the 4\u2010\u03b2\u2010OHC\/cholesterol ratio. Genotyping of relevant\n                      <jats:italic>CYP3A4\/5<\/jats:italic>\n                      gene variants was carried out. Pharmacokinetic parameters were estimated using PKanalix software. Simple and multiple linear regressions were performed\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nineteen patients were included with median age of 66\u2009years (range 44\u201377). Pharmacokinetic parameters were comparable to prior reporting. The 4\u2010\u03b2\u2010OHC\/cholesterol ratio showed a significant positive association with imatinib clearance, explaining 30% of variance. No significant association was found between CYP3A4 activity and N\u2010desmethyl\u2010imatinib area under the concentration time\u2013curve (AUC)\/imatinib AUC ratio. Single\u2010point sampling of imatinib at 3\u20134\u2009h post\u2010dose correlated better with AUC\n                      <jats:sub>0<\/jats:sub>\n                      <jats:sub>\u201324h<\/jats:sub>\n                      than trough concentrations. CYP3A4\/5 genotype assessment was limited by low patient numbers\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first study investigating 4\u2010\u03b2\u2010OHC as a biomarker for CYP3A4 activity in imatinib\u2010treated leukaemia patients, demonstrating clinically meaningful associations with imatinib clearance and supporting further development of this personalized therapy approach.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70622","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:40:47Z","timestamp":1780015247000},"page":"3375-3386","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic profiling of imatinib in relation to CYP3A4 activity in leukaemia patients"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4997-2914","authenticated-orcid":false,"given":"Anna Sofie Buhl","family":"Rasmussen","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"},{"name":"Pediatric Oncology Research Laboratory Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde R\u00f8nne","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"},{"name":"Pediatric Oncology Research Laboratory Copenhagen University Hospital, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0578-3887","authenticated-orcid":false,"given":"Cecilie 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