Clinical Pharmacokinetics and Pharmacodynamics of Dasatinib
- 29 February 2020
- journal article
- review article
- Published by Springer Science and Business Media LLC in Clinical Pharmacokinetics
- Vol. 59 (7), 849-856
- https://doi.org/10.1007/s40262-020-00872-4
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.Keywords
This publication has 41 references indexed in Scilit:
- Differential effects of dosing regimen on the safety and efficacy of dasatinib: retrospective exposure–response analysis of a Phase III studyClinical Pharmacology: Advances and Applications, 2013
- Phase I Trial, Pharmacokinetics, and Pharmacodynamics of Vandetanib and Dasatinib in Children with Newly Diagnosed Diffuse Intrinsic Pontine GliomaClinical Cancer Research, 2013
- Pharmacokinetics of dasatinib for Philadelphia-positive acute lymphocytic leukemia with acquired T315I mutationJournal of Hematology & Oncology, 2012
- Phase I and pharmacokinetic study of dasatinib and cetuximab in patients with advanced solid malignanciesInvestigational New Drugs, 2011
- Pediatric Phase I Trial and Pharmacokinetic Study of Dasatinib: A Report From the Children's Oncology Group Phase I ConsortiumJournal of Clinical Oncology, 2011
- Phase I Study of the Effect of Gastric Acid pH Modulators on the Bioavailability of Oral Dasatinib in Healthy SubjectsThe Journal of Clinical Pharmacology, 2009
- Characterization of Dasatinib and Its Structural Analogs as CYP3A4 Mechanism-Based Inactivators and the Proposed Bioactivation PathwaysDrug Metabolism and Disposition, 2009
- Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome–positive leukemiaBlood, 2008
- Identification of the Human Enzymes Involved in the Oxidative Metabolism of Dasatinib: An Effective Approach for Determining Metabolite Formation KineticsDrug Metabolism and Disposition, 2008
- Overriding Imatinib Resistance with a Novel ABL Kinase InhibitorScience, 2004