Clinical Pharmacokinetic and Pharmacodynamic Profile of Lenvatinib, an Orally Active, Small-Molecule, Multitargeted Tyrosine Kinase Inhibitor

AbstractLenvatinib is a multikinase inhibitor that targets vascular endothelial growth factor (VEGF) receptors 1 –3, fibroblast growth factor receptors 1–4, platelet-derived growth factor receptor-alpha, and RET and KIT proto-oncogenes. Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer in the United States (US), European Union (EU), Canada, Japan, and Switzerl and. It is also approved in combination with everolimus for the treatment of advanced renal cell carcinoma following ≥1 VEGF-targeted treatment in the US and EU. In addition, lenvatinib is under investigation for the treatment of hepatocellular carcinoma. As lenvatinib becomes more widely availab le, a better understanding of its pharmacokinetic profile has become increasingly important. Following oral administration, lenvatinib is absorbed rapidly and is metabolized extensively prior to excretion. This metabolism is mediated by multiple pathways, and several metabolites of lenvatinib have b een identified. The effect of food intake on lenvatinib exposure has also been studied and was found to not significantly influence overall exposure to the drug. Exposure to lenvatinib is increased in patients with severe hepatic impairment, indicating that dose reduction must be considered for thos e patients. The findings summarized here indicate that the clinical pharmacokinetic and pharmacodynamic profile for lenvatinib are predictable, with a dose-independent absorption and ...
Source: European Journal of Drug Metabolism and Pharmacokinetics - Category: Drugs & Pharmacology Source Type: research