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Article Dans Une Revue Expert Opinion on Drug Metabolism and Toxicology Année : 2021

Interactions of janus kinase inhibitors with drug transporters and consequences for pharmacokinetics and toxicity

Résumé

Introduction: Janus kinase inhibitors (JAKinibs) constitute an emerging and promising pharmacological class of anti-inflammatory or anti-cancer drugs, used notably for the treatment of rheumatoid arthritis and some myeloproliferative neoplasms. Areas covered: This review provides an overview of the interactions between marketed JAKinibs and major uptake and efflux drug transporters. Consequences regarding pharmacokinetics, drug-drug interactions and toxicity are summarized. Expert opinion: JAKinibs interact in vitro with transporters in various ways, as inhibitors or as substrates of transporters or as regulators of transporter expression. This may theoretically result in drug-drug interactions (DDIs), with JAKinibs acting as perpetrators or as victims, or in toxicity, via impairment of thiamine transport. Clinical significance in terms of DDIs for JAKinib-transporter interactions remains however poorly documented. In this context, the in vivo unbound concentration of JAKinibs is likely a key parameter to consider for evaluating the clinical relevance of JAKinibs-mediated transporter inhibition. Additionally, the interplay with drug metabolism as well as possible interactions with transporters of emerging importance and time-dependent inhibition have to be taken into account. The role drug transporters may play in controlling cellular JAKinib concentrations and efficacy in target cells is also an issue of interest.

Dates et versions

hal-03095585 , version 1 (04-01-2021)

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Citer

Karima Alim, Arnaud Bruyère, Alain Lescoat, Elodie Jouan, Valérie Lecureur, et al.. Interactions of janus kinase inhibitors with drug transporters and consequences for pharmacokinetics and toxicity. Expert Opinion on Drug Metabolism and Toxicology, 2021, 17 (3), pp.259-271. ⟨10.1080/17425255.2021.1862084⟩. ⟨hal-03095585⟩
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