Skip to main content

ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1438259
This article is part of the Research Topic Drug Metabolism and Transport: The Frontier of Personalized Medicine Volume II View all 9 articles

Effects of three flavonoids on the metabolism of lenvatinib

Provisionally accepted
Jinzhao Yang Jinzhao Yang 1Jie Chen Jie Chen 2Qingqing Li Qingqing Li 2Ren-ai Xu Ren-ai Xu 2*Xiaohai Chen Xiaohai Chen 3
  • 1 Wenzhou People’s Hospital, Wenzhou, Zhejiang Province, China
  • 2 First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  • 3 Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    Lenvatinib is a first-line therapy for the treatment of hepatocellular carcinoma (HCC), an active multi-target tyrosine kinase inhibitor (TKI). The interaction between Traditional Chinese Medicine (TCM) and chemicals has increasingly become a research hotspot. The objective of this study was to pinpoint the effects of three flavonoids on the metabolism of lenvatinib. Enzyme reaction system was established and optimized in vitro, and in vivo experiments were conducted in Sprague-Dawley (SD) rats, where the analytes were detected by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). We found that among three flavonoids, luteolin and myricetin had strong inhibitory effects on lenvatinib metabolism, with half-maximal inhibitory concentration (IC50) values of 11.36 ± 0.46 µM and 11.21 ± 0.81 µM in RLM, respectively, and 6.89 ± 0.43 µM and 12.32 ± 1.21 µM in HLM, respectively. In SD rats, the combined administration of lenvatinib and luteolin obviously expanded the exposure to lenvatinib; however, co-administered with myricetin did not have any changes, which may be due to the poor bioavailability of myricetin in vivo. Furthermore, the inhibitory type of luteolin on lenvatinib showed an un-competitive in RLM and a mixed in HLM. Collectively, flavonoids with liver protection, especially luteolin, may inhibit lenvatinib metabolism in vitro and in vivo.

    Keywords: Hepatocellular Carcinoma, Lenvatinib, Flavonoids, Luteolin, DDIs

    Received: 25 May 2024; Accepted: 26 Jul 2024.

    Copyright: © 2024 Yang, Chen, Li, Xu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ren-ai Xu, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.