Pharmacokinetics and excretion of 14C-lenvatinib in patients with advanced solid tumors or lymphomas

Anne Charlotte Dubbelman, Hilde Rosing, Cynthia Nijenhuis, Alwin D.R. Huitema, Marja Mergui-Roelvink, Anubha Gupta, David Verbel, Gary Thompson, Robert Shumaker, Jan H.M. Schellens, Jos H. Beijnen

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

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 14C-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.

Original languageEnglish
Pages (from-to)233-240
Number of pages8
JournalInvestigational New Drugs
Volume33
Issue number1
DOIs
Publication statusPublished - Feb 2015
Externally publishedYes

Keywords

  • E7080
  • Excretion
  • Lenvatinib
  • Mass balance
  • Pharmacokinetics

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