Effects of Dietary Flavonoids on the Metabolism of Vortioxetine and its Potential Mechanism

  • Authors: Lin Y.1, Wang Y.2, Ye Z.3, Gao N.4, Xu X.5, Weng Q.6, Xu R.7, Ye L.8
  • Affiliations:
    1. Department of Pharmacy,, The Third Affiliated Hospital of Shanghai University (Wenzhou People's Hospital), The Third Clinical Institute Affiliated to Wenzhou Medical University
    2. Basic Medicine College,, Renji College of Wenzhou Medical University
    3. School of Pharmaceutical Sciences, Institute of Molecular Toxicology and Pharmacology, Wenzhou Medical University
    4. School of Pharmaceutical Sciences, Institute of Molecular Toxicology and Pharmacology,, Wenzhou Medical University
    5. Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University
    6. Department of Pharmacy,, The Third Affiliated Hospital of Shanghai University (Wenzhou People's Hospital), The Third Clinical Institute Affiliated to Wenzhou Medical University,
    7. Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province,, The First Affiliated Hospital of Wenzhou Medical University
    8. Procurement Department, The First Affiliated Hospital of Wenzhou Medical University
  • Issue: Vol 31, No 23 (2024)
  • Pages: 3624-3630
  • Section: Anti-Infectives and Infectious Diseases
  • URL: https://rjmseer.com/0929-8673/article/view/645225
  • DOI: https://doi.org/10.2174/0929867330666230607104411
  • ID: 645225

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Abstract

Introduction:Quercetin and apigenin are two common dietary flavonoids widely found in foods and fruits. Quercetin and apigenin can act as the inhibitors of CYP450 enzymes, which may affect the pharmacokinetics of clinical drugs. Vortioxetine (VOR), approved for marketing by the Food and Drug Administration (FDA) in 2013, is a novel clinical drug for treating major depressive disorder (MDD).

Objective:This study aimed to evaluate the effects of quercetin and apigenin on the metabolism of VOR in in vivo and in vitro experiments.

Method:Firstly, 18 Sprague-Dawley rats were randomly divided into three groups: control group (VOR), group A (VOR + 30 mg/kg quercetin) and group B (VOR + 20 mg/kg apigenin). We collected the blood samples at different time points before and after the final oral administration of 2 mg/kg VOR. Subsequently, we further used rat liver microsomes (RLMs) to investigate the half-maximal inhibitory concentration (IC50) of the metabolism of vortioxetine. Finally, we evaluated the inhibitory mechanism of two dietary flavonoids on VOR metabolism in RLMs.

Results:In animal experiments, we found AUC (0-∞) (area under the curve from 0 to infinity) and CLz/F (clearance) to be obviously changed. Compared to controls, AUC (0-∞) of VOR in group A and group B was 2.22 and 3.54 times higher, respectively, while CLz/F of VOR in group A and group B was significantly decreased down to nearly two-fifth and one-third. In in vitro studies, the IC50 value of quercetin and apigenin in the metabolic rate of vortioxetine was 5.323 µM and 3.319 µM, respectively. Ki value of quercetin and apigenin was found to be 0.040 and 3.286, respectively, and the αKi value of quercetin and apigenin was 0.170 and 2.876 µM, respectively.

Conclusion:Quercetin and apigenin exhibited inhibitory effects on the metabolism of vortioxetine in vivo and in vitro. Moreover, quercetin and apigenin had a mixed mechanism on the metabolism of VOR in RLMs. Thus, we should pay more attention to the combination between these dietary flavonoids and VOR in the future clinical use.

About the authors

Yuxian Lin

Department of Pharmacy,, The Third Affiliated Hospital of Shanghai University (Wenzhou People's Hospital), The Third Clinical Institute Affiliated to Wenzhou Medical University

Email: info@benthamscience.net

Yu Wang

Basic Medicine College,, Renji College of Wenzhou Medical University

Email: info@benthamscience.net

Zhize Ye

School of Pharmaceutical Sciences, Institute of Molecular Toxicology and Pharmacology, Wenzhou Medical University

Email: info@benthamscience.net

Nanyong Gao

School of Pharmaceutical Sciences, Institute of Molecular Toxicology and Pharmacology,, Wenzhou Medical University

Email: info@benthamscience.net

Xinhao Xu

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University

Email: info@benthamscience.net

Qinghua Weng

Department of Pharmacy,, The Third Affiliated Hospital of Shanghai University (Wenzhou People's Hospital), The Third Clinical Institute Affiliated to Wenzhou Medical University,

Email: info@benthamscience.net

Ren-ai Xu

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province,, The First Affiliated Hospital of Wenzhou Medical University

Author for correspondence.
Email: info@benthamscience.net

Lei Ye

Procurement Department, The First Affiliated Hospital of Wenzhou Medical University

Author for correspondence.
Email: info@benthamscience.net

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