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Clinical Pharmacokinetics

Clinical Pharmacokinetics

IF: 4.59
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Pharmacokinetics and Pharmacodynamics of Ruxolitinib: A Review.

Published:1 April 2023 DOI: 10.1007/s40262-023-01225-7 PMID: 37000342
T Y J Appeldoorn, T H Oude Munnink, L M Morsink, M N Lub-de Hooge, D J Touw

Abstract

Background and objective: Ruxolitinib is a tyrosine kinase inhibitor targeting the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways. Ruxolitinib is used to treat myelofibrosis, polycythemia vera and steroid-refractory graft-versus-host disease in the setting of allogeneic stem-cell transplantation. This review describes the pharmacokinetics and pharmacodynamics of ruxolitinib.

Methods: Pubmed, EMBASE, Cochrane Library and web of Science were searched from the time of database inception to march 15, 2021 and was repeated on November 16, 2021. Articles not written in English, animal or in vitro studies, letters to the editor, case reports, where ruxolitinib was not used for hematological diseases or not available as full text were excluded.

Results: Ruxolitinib is well absorbed, has 95% bio-availability, and is bound to albumin for 97%. Ruxolitinib pharmacokinetics can be described with a two-compartment model and linear elimination. Volume of distribution differs between men and women, likely related to bodyweight differences. Metabolism is mainly hepatic via CYP3A4 and can be altered by CYP3A4 inducers and inhibitors. The major metabolites of ruxolitinib are pharmacologically active. The main route of elimination of ruxolitinib metabolites is renal. Liver and renal dysfunction affect some of the pharmacokinetic variables and require dose reductions. Model-informed precision dosing might be a way to further optimize and individualize ruxolitinib treatment, but is not yet advised for routine care due to lack of information on target concentrations.

Conclusion: Further research is needed to explain the interindividual variability of the ruxolitinib?pharmacokinetic variables and to optimize individual treatment.

Substances (2)

Related products
Procduct Name CAS Molecular Formula Supplier Price
Ruxolitinib 941678-49-5 C17H18N6 398 suppliers $25.00-$2757.40
P450 3A4 34 suppliers Inquiry

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