Lenvatinib is an orally available multi-targeted
tyrosine kinase inhibitor with anti-angiogenic and antitumor activity. To get more insight into the disposition of
lenvatinib, a mass balance study was performed in patients with advanced solid
tumors. A single oral 24 mg (100 μCi) dose of (14)C-lenvatinib was administered to six patients, followed by collection of blood, plasma, urine and feces for 7 to 10 days. The collected material was analyzed for total radioactivity, unchanged
lenvatinib and selected metabolites. The safety and antitumor effect of a daily oral dose of 24 mg non-labeled
lenvatinib were assessed in the extension phase of the study. Peak plasma concentrations of
lenvatinib and total radioactivity were reached 1.6 and 1.4 h after administration, respectively, and their terminal phase half-lifes were 34.5 and 17.8 h, respectively. Unchanged
lenvatinib systemic exposure accounted for 60 % of the total radioactivity in plasma. Peak concentrations of the analyzed metabolite were over 700-fold lower than the peak plasma concentration of
lenvatinib. Ten days after the initial dose, the geometric mean (± CV) recovery of administered dose was 89 % ±10 %, with 64 % ±11 % recovered in feces and 25 % ±18 % in urine. Unchanged
lenvatinib in urine and feces accounted for 2.5 % ±68 % of the administered dose, indicating a major role of metabolism in the elimination of
lenvatinib. In conclusion,
lenvatinib is rapidly absorbed and extensively metabolized, with subsequent excretion in urine and, more predominantly, in feces. Additionally,
lenvatinib showed acceptable safety and preliminary antitumor activity.