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Effects of three flavonoids on the metabolism of lenvatinib

Jinzhao Yang1, Jie Chen2, Qingqing Li2

  • 1Wenzhou People's Hospital, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, China.

Frontiers in Pharmacology
|September 4, 2024
PubMed

Insights

Luteolin and myricetin inhibit lenvatinib metabolism in vitro. Luteolin increased lenvatinib exposure in rats, suggesting potential drug interactions with Traditional Chinese Medicine components.

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Hepatocellular Carcinoma (HCC) Research

Background:

  • Lenvatinib is a key first-line therapy for hepatocellular carcinoma (HCC).
  • Interactions between Traditional Chinese Medicine (TCM) and chemical drugs are a growing area of research.
  • Understanding how TCM components affect lenvatinib metabolism is crucial for optimizing treatment.

Purpose of the Study:

  • To investigate the impact of three flavonoids on lenvatinib metabolism.
  • To determine the in vitro and in vivo effects of specific flavonoids on lenvatinib pharmacokinetics.
  • To identify potential drug-herb interactions relevant to HCC treatment.

Main Methods:

  • Established and optimized in vitro enzyme reaction systems.
  • Conducted in vivo experiments using Sprague-Dawley (SD) rats.
  • Analyzed drug concentrations using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).

Main Results:

  • Luteolin and myricetin demonstrated significant inhibition of lenvatinib metabolism in both rat liver microsomes (RLM) and human liver microsomes (HLM).
  • In vivo, luteolin administration increased lenvatinib exposure in rats, while myricetin showed no significant effect, possibly due to bioavailability differences.
  • Luteolin exhibited un-competitive inhibition in RLM and mixed inhibition in HLM regarding lenvatinib metabolism.

Conclusions:

  • Flavonoids, particularly luteolin, can inhibit lenvatinib metabolism both in vitro and in vivo.
  • Luteolin's potential to alter lenvatinib pharmacokinetics warrants consideration in clinical settings.
  • These findings highlight the importance of evaluating TCM-drug interactions for HCC patients.
Keywords:
DDIsflavonoidshepatocellular carcinomalenvatinibluteolin

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