COMMON BRAND NAME(S): Gleevec
GENERIC NAME(S): IMATINIB MESYLATE
Description: Imatinib is a tyrosine kinase inhibitor that blocks proliferation and induces apoptosis in BCR-ABL positive cell lines, as well as fresh leukaemic cells from Philadelphia chromosome positive CML. Imatinib also inhibits receptor kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-kit, PDGF- and SCF-mediated cellular events.
Absorption: Rapidly and well absorbed from the GI tract. Mean bioavailability: Approx 98%. Time to peak plasma concentration: 2-4 hr.
Distribution: Plasma protein binding: Approx 95%.
Metabolism: Primarily via CYP3A4 isoenzyme and to a lesser extent via CYP1A2, CYP2D6, CYP2C9 and CYP2C19 isoenzymes. N-demethylated piperazine derivative (active metabolite).
Excretion: Via faeces (68%) and urine (13%) w/in 7 days; excreted mostly as metabolites, w/ 25% as unchanged drug. Elimination half-life: Approx 18 hr (imatinib); approx 40 hr (N-demethylated piperazine derivative).