Clinical Pharmacokinetics and Pharmacodynamics of Dasatinib.
Fiche publication
Date publication
février 2020
Journal
Clinical pharmacokinetics
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BILGER Karin, Dr AME Shanti
Tous les auteurs :
Levêque D, Becker G, Bilger K, Natarajan-Amé S
Lien Pubmed
Résumé
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, H-receptor blockers, proton pump inhibitors), and dasatinib is also subject to drug interactions with CYP3A4 inducers or inhibitors.
Référence
Clin Pharmacokinet. 2020 Feb 29;: