Ruxolitinib Pharmacokinetics and Exposure–Toxicity Relationship in Hematologic Malignancies and Immune‐Mediated Diseases: A Prospective Observational Study
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Le résumé fourni par la source
Ruxolitinib pharmacokinetics (PK) has been characterized in clinical trials but remains poorly documented in real‐world practice. This project aimed to investigate ruxolitinib PK in routine clinical practice, identify factors driving its variability, and explore exposure–response relationships to assess the potential role of therapeutic drug monitoring. In total, 221 steady‐state 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® 2024R1 (Lixoft, France). Model‐based simulations were used to predict trough concentration ( C min ) and the area under the concentration–time curve over 24 h (AUC 24 ) 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‐subject variability in clearance (45%). Strong cytochrome (CYP) 3A4 or dual CYP2C9/CYP3A4 inhibitors reduced clearance by 39%. At 10 mg twice daily, model‐based simulations showed CYP inhibitors increased median C min and AUC 24 by 2.9‐ and 1.7‐fold, respectively. Still, no significant exposure–efficacy relationship was identified. However, higher ruxolitinib exposure tended to be associated with increased toxicity in the overall population ( C min and AUC 24 , P ≈0.02–0.03). In clinical practice, ruxolitinib exposure shows substantial variability and is strongly affected by strong CYP inhibitors that are frequently co‐administered. Whilst no clear exposure–efficacy relationship was observed, higher exposure was linked to increased toxicity risk, arguing for careful dose adjustment.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Ruxolitinib Pharmacokinetics and Exposure–Toxicity Relationship in Hematologic Malignancies and Immune‐Mediated Diseases: A Prospective Observational Study
- Date Crossref
- 24/06/2026
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Lausanne Service of Clinical Pharmacology pays non établi dans la noticeUniversité ou école supérieure
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University Hospital of Bern pays non établi dans la noticeÉtablissement de santé
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Hôpital de Morges pays non établi dans la noticeÉtablissement de santé
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University Hospital of Basel pays non établi dans la noticeÉtablissement de santé
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HES-SO University of Applied Sciences and Arts Western Switzerland pays non établi dans la noticeUniversité ou école supérieure
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Bern University Hospital and University of Bern Bern Switzerland Department of Hematology and Central Hematology Laboratory Inselspital pays non établi dans la noticeUniversité ou école supérieure
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Service of Hematology Hospital of Morges Morges Switzerland pays non établi dans la noticeÉtablissement de santé
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Division of Hematology Basel University Hospital and University of Basel Basel Switzerland pays non établi dans la noticeUniversité ou école supérieure
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Institute of Pharmaceutical Sciences of Western Switzerland University of Geneva pays non établi dans la noticeUniversité ou école supérieure
Service of Clinical Pharmacology — University of Lausanne, University Hospital of Bern et Hôpital de Morges, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.