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A mechanism-based understanding of altered drug pharmacokinetics by gut microbiota

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Abstract

Background

Pharmacomicrobiomics, which has recently emerged as a new strategy for personalized medicine, is the investigation of the influence of microbial variability on drug pharmacokinetics, efficacy, and safety. The roles of gut microbiota in drug pharmacokinetics should be thoroughly investigated, given the significant implications of gut microbiota in humans.

Area covered

In this paper, we provide a mechanism-based review of the impact of the gut microbiota on drug pharmacokinetics, primarily based on drug metabolism and transporters. The main mechanisms presented here are the direct metabolism of drugs by gut microbiota activity, modulation of relevant gene expression, and competitive inhibition using their metabolites. We also present the limitations of current research and provide perspectives for future investigations.

Expert opinion

Although prominent advances in research have paved the way to link gut microbiota and drug pharmacokinetics, there are still some limitations and restrictions to understand their intricate association. Particular attention should be paid to studies using germ-free or antibiotic-treated animals to determine associations between gut microbiota and drug pharmacokinetics. Technical limitations may also hamper advances in research on microbiota, and the expanded use of -omics techniques is expected to further improve the accuracy and efficiency of microbial investigations. More translational research that links clinical and in vitro/pre-clinical studies is warranted to facilitate microbiome-based personalized therapy.

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Acknowledgements

This research was supported by a Grant from the KRIBB Research Initiative Program, the Technology Innovation Program (Nos. 20009774) funded by the Ministry of Trade, Industry, and Energy (MOTIE, Korea), and the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2021R1I1A3056261).

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  1. Aneela Gulnaz and Ji-Eun Chang have contributed equally to this manuscript.

Authors and Affiliations

  1. College of Pharmacy, Woosuk University, Wanju, 55338, Korea

    Aneela Gulnaz & Yoon-Jee Chae

  2. College of Pharmacy, Dongduk Women’s University, Seoul, 02748, Korea

    Ji-Eun Chang

  3. College of Pharmacy, Gachon University, Incheon, 21936, Korea

    Han-Joo Maeng

  4. College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 41566, Korea

    Kwang-Hee Shin

  5. Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, 28116, Korea

    Kyeong-Ryoon Lee

  6. Department of Bioscience, University of Science and Technology, Daejeon, 34113, Korea

    Kyeong-Ryoon Lee

  7. Research Institute of Pharmaceutical Sciences, Woosuk University, Wanju, 55338, Korea

    Yoon-Jee Chae

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Gulnaz, A., Chang, JE., Maeng, HJ. et al. A mechanism-based understanding of altered drug pharmacokinetics by gut microbiota. J. Pharm. Investig. 53, 73–92 (2023). https://doi.org/10.1007/s40005-022-00600-z

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