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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.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The Role of Gut Bacteria in Tacrolimus Disposition./
Author:	Guo, Yukuang.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
Description:	157 p.
Notes:	Source: Dissertations Abstracts International, Volume: 83-02, Section: B.
Contained By:	Dissertations Abstracts International83-02B.
Subject:	Microbiology. -
Online resource:	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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245 1 4 $a The Role of Gut Bacteria in Tacrolimus Disposition.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2021
300 $a 157 p.
500 $a Source: Dissertations Abstracts International, Volume: 83-02, Section: B.
500 $a Advisor: Jeong, Hyunyoung;Lee, Hyunwoo.
502 $a Thesis (Ph.D.)--University of Illinois at Chicago, 2021.
506 $a This item must not be sold to any third party vendors.
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.
590 $a School code: 0799.
650 4 $a Microbiology. $3 536250
650 4 $a Molecular biology. $3 517296
650 4 $a Genetics. $3 530508
650 4 $a Pharmacology. $3 634543
650 4 $a Physiology. $3 518431
650 4 $a Nitrates. $3 914879
650 4 $a Organic chemicals. $3 3560375
650 4 $a Plasma. $3 877619
650 4 $a Glycoproteins. $3 667972
650 4 $a Nuclear magnetic resonance--NMR. $3 3560258
650 4 $a Bacteria. $3 550366
650 4 $a Inflammatory bowel disease. $3 3560376
650 4 $a Influenza. $3 924085
650 4 $a Scientific imaging. $3 3560377
650 4 $a E coli. $3 3556834
650 4 $a Metabolism. $3 541349
650 4 $a Small intestine. $3 3560378
650 4 $a Drug dosages. $3 3557732
650 4 $a Bioavailability. $3 875104
650 4 $a Proteins. $3 558769
650 4 $a Mass spectrometry. $3 551172
650 4 $a Feces. $3 544385
650 4 $a Permeability. $3 915594
650 4 $a Antibiotics. $3 670318
650 4 $a Colon. $3 3560379
650 4 $a Microbiota. $3 3310213
650 4 $a Enzymes. $3 520899
650 4 $a Metabolites. $3 683644
650 4 $a Polymorphism. $3 3560380
653 $a Gut bacteria
653 $a Tacrolimus
653 $a Metabolism
690 $a 0410
690 $a 0307
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690 $a 0719
710 2 $a University of Illinois at Chicago. $b Pharmaceutical Sciences. $3 3560374
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791 $a Ph.D.
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