Impact of Gut Microbiota on the Pharmacokinetics of Glycyrrhizic Acid in Yokukansan, a Kampo Medicine

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  • Ishida Tomoaki
    Department of Pharmacy, Kochi Medical School Hospital
  • Jobu Kohei
    Department of Pharmacy, Kochi Medical School Hospital
  • Kawada Kei
    Department of Pharmacy, Kochi Medical School Hospital Graduate school of Integrated Arts and Sciences, Kochi University
  • Morisawa Shumpei
    Department of Pharmacy, Kochi Medical School Hospital Graduate school of Integrated Arts and Sciences, Kochi University
  • Kawazoe Tetsushi
    Department of Pharmacy, Kochi Medical School Hospital Graduate school of Integrated Arts and Sciences, Kochi University
  • Shiraishi Hisashi
    Department of Pharmacy, Kochi Medical School Hospital
  • Fujita Hiroko
    Department of Pharmacy, Kochi Medical School Hospital
  • Nishimura Satomi
    Department of Pharmacy, Kochi Medical School Hospital
  • Kanno Hitomi
    Tsumura Advanced Technology Research Laboratories, Tsumura & Co.
  • Nishiyama Mitsue
    Tsumura Advanced Technology Research Laboratories, Tsumura & Co.
  • Ogawa Kazuo
    Tsumura Advanced Technology Research Laboratories, Tsumura & Co.
  • Morita Yasuyo
    Department of Pharmacy, Kochi Medical School Hospital
  • Hanazaki Kazuhiro
    Department of Surgery, Kochi Medical School Hospital
  • Miyamura Mitsuhiko
    Department of Pharmacy, Kochi Medical School Hospital Graduate school of Integrated Arts and Sciences, Kochi University

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<p>Individual differences in gut microbiota can affect the pharmacokinetics of drugs. Yokukansan is a traditional Japanese kampo medicine used to treat peripheral symptoms of dementia and delirium. A study examining the pharmacokinetics of the components of yokukansan reported large individual differences in the pharmacokinetics of glycyrrhizic acid (GL). It is known that GL is metabolized by intestinal bacteria to glycyrrhetinic acid (GA), which is absorbed in the gastrointestinal tract. Thus, the gut microbiota may affect GL pharmacokinetics. We aimed to clarify the relationship between the gut microbiota composition and pharmacokinetics of GL in yokukansan. Mice were orally administered yokukansan, following the administration of various antibiotics, and the plasma concentration of GA and composition of gut microbiota were measured. The GA plasma concentration was low in mice treated with amoxicillin and vancomycin. The composition of gut microbiota revealed a different pattern from that of the control group. Mice with low plasma levels of GA had lower levels of the phylum Bacteroides and Firmicutes. Additionally, bacteria, such as those belonging to the genera Parabaceroides, Bacteroides, Ruminococcus and an unknown genus in families Lachnospiraceae and Ruminococcaceae, exerted positive correlations between the gene copies and plasma GA levels. These bacteria may contribute to the absorption of GA in the gastrointestinal tract, and multiple bacteria may be involved in GL pharmacokinetics. The pharmacokinetics of GL may be predicted by evaluating the composition of gut bacteria, rather than by evaluating the amount of a single bacterium.</p>

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