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Clinical Pharmacokinetics and Pharmacodynamics of Dasatinib

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Abstract

Dasatinib is an oral, once-daily tyrosine kinase inhibitor used in the treatment of chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaemia. Dasatinib is rapidly absorbed, with the time for maximal serum concentration varying between 0.25 and 1.5 h. Oral absorption is not affected by food. The absolute bioavailability of dasatinib in humans is unknown due to the lack of an intravenous formulation preventing calculation of the reference exposure. Dasatinib is eliminated through cytochrome P450 (CYP) 3A4-mediated metabolism, with a terminal half-life of 3–4 h. Based on total radioactivity, only 20% of the oral dose (100 mg) is recovered unchanged in faeces (19%, including potential non-absorption) and urine (1%) after 168 h. Dasatinib pharmacokinetics are not influenced by age (children, and adults up to 86 years of age), race and renal insufficiency. Dasatinib absorption is decreased by pH-modifying agents (antacids, H2-receptor blockers, proton pump inhibitors), and dasatinib is also subject to drug interactions with CYP3A4 inducers or inhibitors.

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Acknowledgements

The authors acknowledge the reviewers for their helpful comments. This paper is dedicated to the memory of Jeanne Wihlm.

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Authors and Affiliations

  1. Pharmacy, Hôpital Hautepierre, Avenue Molière, 67000, Strasbourg, France

    Dominique Levêque & Guillaume Becker

  2. Hematology, Hôpital Hautepierre, Avenue Molière, 67000, Strasbourg, France

    Karin Bilger & Shanti Natarajan-Amé

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  1. Dominique Levêque
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Correspondence to Dominique Levêque.

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Dominique Levêque, Guillaume Becker, Karin Bilger, and Shanti Natarajan-Amé have no conflicts of interest to declare in relation to the subject matter. No writing assistance was utilised in the production of this manuscript.

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Levêque, D., Becker, G., Bilger, K. et al. Clinical Pharmacokinetics and Pharmacodynamics of Dasatinib. Clin Pharmacokinet 59, 849–856 (2020). https://doi.org/10.1007/s40262-020-00872-4

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