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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1526159
This article is part of the Research Topic Drug Metabolism and Transport: The Frontier of Personalized Medicine Volume II View all 19 articles
Inhibitory effect of luteolin on the metabolism of vandetanib in vivo and in vitro
Provisionally accepted- First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
This study aimed to examine the potential drug-drug interaction (DDI) between vandetanib and luteolin in vivo and in vitro, with the objective of establishing a scientific foundation for their appropriate utilization in clinical settings. Sprague-Dawley (SD) rats were randomly divided into two groups: a control group (vandetanib administered by gavage alone) and an experimental group (vandetanib and luteolin administered together). A series of blood samples were collected at different time intervals. The plasma concentrations of vandetanib and its metabolite N-demethyl vandetanib in rats were determined using an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Incubation systems were set up with rat liver microsomes (RLM) and human liver microsomes (HLM) to measure the Michaelis-Menten constant (Km) and half maximum inhibitory concentration (IC50) values. Additionally, the inhibitory mechanism of luteolin on vandetanib was also investigated. Ultimately, the molecular mechanism of inhibition was examined through the utilization of molecular docking techniques. In vivo animal experiment results showed that compared with the control group, the AUC(0-t) and Cmax of vandetanib in the experimental group were significantly increased. The findings from the in vitro experiments revealed that luteolin exhibited a moderate inhibitory effect on the metabolism of vandetanib. The IC50 values for RLM and HLM were determined to be 8.56 μM and 15.84 μM, respectively. The identified inhibition mechanism was classified as mixed. This study utilized molecular docking analysis to provide additional evidence supporting the competitive inhibition of luteolin on vandetanib in CYP3A4. The data presented in our study indicated a potential interaction between vandetanib and luteolin, which may necessitate the need for dose adjustment during their coadministration in clinical settings.
Keywords: vandetanib, Luteolin, Drug-Drug Interaction, UPLC-MS/MS, molecular docking vandetanib, molecular docking
Received: 11 Nov 2024; Accepted: 12 Feb 2025.
Copyright: © 2025 Shen, Hong, Wu, Chen, Xia, Xu, Lin and Shi. 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:
Fengsheng Hong, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Hualu Wu, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Guanyang Lin, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Lu Shi, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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