Chapter Four - Dasatinib

Abstract

Dasatinib (Sprycel®), a second-generation TKI, has been shown to be effective as an anticancer drug in the treatment of patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia who are resistant or intolerant to imatinib. Several methods of gefitinib synthesis are included in this review. UV spectroscopy of dasatinib showed a λmax of approximately 320-330nm, and IR spectroscopy principal peaks were observed at 3418 (NH), 3200 (OH), 1620 (CO), 1582 (CC and CN), 1513 (CHCH) cm(-1). Characteristic NH peaks were observed in nuclear magnetic resonance (NMR) spectroscopy at 11.47 and 9.88ppm. The molecular mass was observed at m/z=487.3((35)Cl) and 488.9((37)Cl) (molecular weight=487.15) and the fragmentation pattern was studied using ion trap mass spectrometry. In addition, different analytical methods for determination of dasatinib are also described in this review. Pharmacokinetically, dasatinib is rapidly absorbed after oral administration where the solubility is dependent on pH. Dasatinib extensively binds to human plasma proteins by approximately 96%. In leukemic patient, the calculated apparent volume of distribution for dasatinib was 2502L and the estimated elimination half-life was approximately 3-5h. Dasatinib is metabolized in humans markedly by CYP3A4 to active metabolites and by phase II drug-metabolizing enzymes, such as UDP glucuronosyltransferase. Dasatinib is mainly eliminated via the feces (85%), of which relatively small amount of dasatinib is excreted unchanged as intact drug (19%). Most of the adverse effects associated with dasatinib therapy are mild to moderate in severity and are usually reversible and manageable with appropriate intervention, such as cardiac failure, hypertension, and coronary artery disease.