Metabolism and Disposition of Dasatinib after Oral Administration to Humans

• Published in: Drug metabolism and disposition 2008-07, Vol.36 (7), p.1357-1364
• Main Authors: Christopher, Lisa J., Cui, Donghui, Wu, Chiyuan, Luo, Roger, Manning, James A., Bonacorsi, Samuel J., Lago, Michael, Allentoff, Alban, Lee, Francis Y.F., McCann, Betty, Galbraith, Susan, Reitberg, Donald P., He, Kan, Barros, Anthony, Blackwood-Chirchir, Anne, Humphreys, W. Griffith, Iyer, Ramaswamy A.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - blood; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - urine; Biological and medical sciences; Dasatinib; Humans; Medical sciences; Pharmacology. Drug treatments; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - blood; Protein Kinase Inhibitors - pharmacokinetics; Protein Kinase Inhibitors - urine; Pyrimidines - administration & dosage; Pyrimidines - blood; Pyrimidines - pharmacokinetics; Pyrimidines - urine; Thiazoles - administration & dosage; Thiazoles - blood; Thiazoles - pharmacokinetics; Thiazoles - urine
• ISSN: 0090-9556; 1521-009X
• DOI: 10.1124/dmd.107.018267

SPRYCEL (dasatinib, BMS-354825; Bristol-Myers Squibb, Princeton, NJ), a multiple kinase inhibitor, is currently approved to treat chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia tumors in patients who are resistant or intolerant to imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). After a 100-mg single p.o. dose of [14C]dasatinib to healthy volunteers, the radioactivity was rapidly absorbed (Tmax ∼0.5 h). Both dasatinib and total radioactivity (TRA) plasma concentrations decreased rapidly with elimination half-life values of