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Impact of gut microbiota on drug metabolism: an update for safe and effective use of drugs

Archives of Pharmacal Research volume 40, pages 1345–1355 (2017)Cite this article

Abstract

The intestinal mucosa and liver have long been considered as the main sites of drug metabolism, and the contribution of gut microbiota to drug metabolism has been under-estimated. However, it is now generally accepted that the gut microbiota plays an important role in drug metabolism prior to drug absorption or during enterohepatic circulation via various microbial enzymatic reactions in the intestine. Moreover, some drugs are metabolized by gut microbiota to specific metabolite(s) that cannot be formed in the liver. More importantly, the metabolism of drugs by gut microbiota prior to absorption can alter the systemic bioavailability of certain drugs. Therefore, understanding drug metabolism by gut microbiota is critical for explaining changes in the pharmacokinetics of drugs, which may cause significant alterations in drug-induced pharmacodynamics and toxicities. In this review, we describe recent progress with regard to the role of metabolism by gut microbiota in some drug-induced alterations of either pharmacological or toxicological effects to emphasize the clinical importance of gut microbiota for safe and effective use of drugs.

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Acknowledgements

This work was supported by grants from National Research Foundation of Korea (NRF-2017R1D1A3B04033313) and from Yeungnam University (214-A-345-027).

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    Affiliations

    1. Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada

      Keumhan Noh

    2. College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea

      You Ra Kang, Mahesh Raj Nepal, Rajina Shakya, Mi Jeong Kang & Tae Cheon Jeong

    3. College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea

      Wonku Kang

    4. College of Pharmacy, Kyungpook National University, Daegu, 41566, Republic of Korea

      Sangkyu Lee

    5. College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea

      Hye Gwang Jeong

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    1. Keumhan Noh
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    Keumhan Noh and You Ra Kang have contributed equally to this work.

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    Noh, K., Kang, Y.R., Nepal, M.R. et al. Impact of gut microbiota on drug metabolism: an update for safe and effective use of drugs. Arch. Pharm. Res. 40, 1345–1355 (2017). https://doi.org/10.1007/s12272-017-0986-y

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    Keywords

    • Gut microbiota
    • Drug metabolism
    • Pharmacokinetics
    • Pharmacodynamics
    • Toxicity