{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:26:45Z","timestamp":1793467605729,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    Ruxolitinib pharmacokinetics (PK) has been characterized in clinical trials but remains poorly documented in real\u2010world practice. This project aimed to investigate ruxolitinib PK in routine clinical practice, identify factors driving its variability, and explore exposure\u2013response relationships to assess the potential role of therapeutic drug monitoring. In total, 221 steady\u2010state ruxolitinib concentrations from 77 adult patients enrolled across several centers in Switzerland were analyzed. Demographic and clinical data were recorded at each visit. Population pharmacokinetic (popPK) analysis was performed with MonolixSuite\u00ae 2024R1 (Lixoft, France). Model\u2010based simulations were used to predict trough concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>min<\/jats:sub>\n                    ) and the area under the concentration\u2013time curve over 24\u2009h (AUC\n                    <jats:sub>24<\/jats:sub>\n                    ) for the recommended dosage regimens, as a function of covariates. An exploratory pharmacokinetic\/pharmacodynamic analysis was conducted in the overall cohort. Ruxolitinib PK was characterized by a marked between\u2010subject variability in clearance (45%). Strong cytochrome (CYP) 3A4 or dual CYP2C9\/CYP3A4 inhibitors reduced clearance by 39%. At 10\u2009mg twice daily, model\u2010based simulations showed CYP inhibitors increased median\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>min<\/jats:sub>\n                    and AUC\n                    <jats:sub>24<\/jats:sub>\n                    by 2.9\u2010 and 1.7\u2010fold, respectively. Still, no significant exposure\u2013efficacy relationship was identified. However, higher ruxolitinib exposure tended to be associated with increased toxicity in the overall population (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>min<\/jats:sub>\n                    and AUC\n                    <jats:sub>24<\/jats:sub>\n                    ,\n                    <jats:italic>P<\/jats:italic>\n                    \u22480.02\u20130.03). In clinical practice, ruxolitinib exposure shows substantial variability and is strongly affected by strong CYP inhibitors that are frequently co\u2010administered. Whilst no clear exposure\u2013efficacy relationship was observed, higher exposure was linked to increased toxicity risk, arguing for careful dose adjustment.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70367","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:11:16Z","timestamp":1782288676000},"page":"753-761","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ruxolitinib Pharmacokinetics and Exposure\u2013Toxicity Relationship in Hematologic Malignancies and Immune\u2010Mediated Diseases: A Prospective Observational Study"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2442-6327","authenticated-orcid":false,"given":"J\u00e9r\u00e9mie","family":"Tachet","sequence":"first","affiliation":[{"name":"Service of Clinical Pharmacology, Department of Medicine Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-185X","authenticated-orcid":false,"given":"Sara C.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Hematology and Central Hematology Laboratory Inselspital, Bern University Hospital and University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2208-2070","authenticated-orcid":false,"given":"Francesco","family":"Grandoni","sequence":"additional","affiliation":[{"name":"Service and Central Laboratory of Hematology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2426-2366","authenticated-orcid":false,"given":"Emmanuel","family":"Haefliger","sequence":"additional","affiliation":[{"name":"Department of Hematology and Central Hematology Laboratory Inselspital, Bern University Hospital and University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3609-4523","authenticated-orcid":false,"given":"Monika","family":"Nagy\u2010Hulliger","sequence":"additional","affiliation":[{"name":"Service of Hematology Hospital of Morges  Morges Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4304-1956","authenticated-orcid":false,"given":"J\u00f6rg P.","family":"Halter","sequence":"additional","affiliation":[{"name":"Division of Hematology Basel University Hospital and University of Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7092-3351","authenticated-orcid":false,"given":"Jakob R.","family":"Passweg","sequence":"additional","affiliation":[{"name":"Division of Hematology Basel University Hospital and University of Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7896-0894","authenticated-orcid":false,"given":"David","family":"Haefliger","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology, Department of Medicine Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Bardinet","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9840-1325","authenticated-orcid":false,"given":"Laurent A.","family":"Decosterd","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology Lausanne University 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