| Indication |
For the treatment of adults with chronic, accelerated, or myeloid
or lymphoid blast phase chronic myeloid leukemia with resistance or
intolerance to prior therapy. Also indicated for the treatment of adults
with Philadelphia chromosome-positive acute lymphoblastic leukemia with
resistance or intolerance to prior therapy. |
| Pharmacodynamics |
Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor |
| Mechanism of action |
Dasatinib, at nanomolar concentrations, inhibits the following
kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and
PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to
multiple conformations of the ABL kinase. In vitro, dasatinib was active
in leukemic cell lines representing variants of imatinib mesylate
sensitive and resistant disease. Dasatinib inhibited the growth of
chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL)
cell lines overexpressing BCR-ABL. Under the conditions of the assays,
dasatinib was able to overcome imatinib resistance resulting from
BCR-ABL kinase domain mutations, activation of alternate signaling
pathways involving the SRC family kinases (LYN, HCK), and multi-drug
resistance gene overexpression. |
| Absorption |
Not Available |
| Volume of distribution |
|
| Protein binding |
96% |
| Metabolism |
Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4 |
| Route of elimination |
Dasatinib is extensively metabolized in humans, primarily by the
cytochrome P450 enzyme 3A4. Elimination is primarily via the feces. |
| Half life |
The overall mean terminal half-life of dasatinib is 3-5 hours. |
| Clearance |
Not Available |
| Toxicity |
Acute overdose in animals was associated with cardiotoxicity. |
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