<p>Lenvatinib is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; platelet-derived growth factor receptor alpha (PDGFR ), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with concurrent inhibition of FGF-receptor substrate 2 (FRS2 ) phosphorylation.<br />
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<strong>Absorption</strong>: The time to peak plasma concentration (Tmax) typically occurred from 1 to 4 hours post-dose. Administration with a high-fat meal (approximately 900 calories of which approximately 55% were from fat, 15% from protein, and 30% from carbohydrates) did not affect the extent of absorption, but decreased the rate of absorption and delayed the median Tmax from 2 hours to 4 hours.<br />
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<strong>Distribution</strong>: In vitro binding of Lenvatinib to human plasma proteins ranged from 98% to 99% at concentrations of 0.3 to 30 &mu;g/mL. The blood-to-plasma concentration ratio ranged from 0.59 to 0.61 at concentrations of 0.1 to 10 &mu;g/mL in vitro.<br />
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<strong>Metabolism</strong>: The main metabolic pathways for Lenvatinib in humans were identified as enzymatic (CYP3A and aldehyde oxidase) and non-enzymatic processes. Excretion: Ten days after a single administration of radiolabeled Lenvatinib, approximately 64% and 25% of the radiolabel were eliminated in the feces and urine, respectively.<br />
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<strong>Elimination</strong>: The terminal elimination half-life of Lenvatinib was approximately 28 hours.</p>