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The Role of Gut Bacteria in Tacrolim...

Guo, Yukuang.

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The Role of Gut Bacteria in Tacrolimus Disposition.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Role of Gut Bacteria in Tacrolimus Disposition./
作者:	Guo, Yukuang.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	157 p.
附註:	Source: Dissertations Abstracts International, Volume: 83-02, Section: B.
Contained By:	Dissertations Abstracts International83-02B.
標題:	Microbiology. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28722820
ISBN:	9798534687361

The Role of Gut Bacteria in Tacrolimus Disposition.
Guo, Yukuang.

The Role of Gut Bacteria in Tacrolimus Disposition. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 157 p.

Source: Dissertations Abstracts International, Volume: 83-02, Section: B.

Thesis (Ph.D.)--University of Illinois at Chicago, 2021.

This item must not be sold to any third party vendors.

Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Tacrolimus exhibits a low and variable oral bioavailability, with an average of 25% of the oral dose reaching the systemic circulation. The major site of drug loss is in the gut, and the gut extraction ratio was reported as 85% and 74% in healthy and liver transplant patients, respectively. However, current known factors including CYP3A4/5 mediated drug metabolism and P-glycoprotein mediated drug efflux does not fully explain the drug loss. This suggest other contributing factors are yet to be well defined. In this project, we examined the possibility of tacrolimus being metabolized by bacteria that contribute to low oral drug exposure. Our results demonstrate bacterial metabolism of tacrolimus as an important elimination pathway in humans. In detail, human gut bacteria can convert tacrolimus to hydroxyl-tacrolimus, a much less active form, through ketone reduction and reduce tacrolimus oral exposure.

ISBN: 9798534687361Subjects--Topical Terms:

536250
Microbiology.
Subjects--Index Terms:

Gut bacteria

The Role of Gut Bacteria in Tacrolimus Disposition.
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520 $a Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Tacrolimus exhibits a low and variable oral bioavailability, with an average of 25% of the oral dose reaching the systemic circulation. The major site of drug loss is in the gut, and the gut extraction ratio was reported as 85% and 74% in healthy and liver transplant patients, respectively. However, current known factors including CYP3A4/5 mediated drug metabolism and P-glycoprotein mediated drug efflux does not fully explain the drug loss. This suggest other contributing factors are yet to be well defined. In this project, we examined the possibility of tacrolimus being metabolized by bacteria that contribute to low oral drug exposure. Our results demonstrate bacterial metabolism of tacrolimus as an important elimination pathway in humans. In detail, human gut bacteria can convert tacrolimus to hydroxyl-tacrolimus, a much less active form, through ketone reduction and reduce tacrolimus oral exposure.
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650 4 $a Nitrates. $3 914879
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