Evidence map›Paper›PMID 35777915›Full record

ArticleJournal of advanced research2022

Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug.

Jing Guo, Ying Xu, Li-Jie Chen, Song-Xia Zhang, Yu-Ligh Liou, Xiao-Ping Chen, Zhi-Rong Tan, Hong-Hao Zhou, Wei Zhang, Yao Chen

Open access · goldAbstract read
In one paragraph

Article in Journal of advanced research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Jing GuoDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.
Ying XuDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.
Li-Jie ChenDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.
Song-Xia ZhangDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.
Yu-Ligh LiouDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.
Xiao-Ping ChenDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.
Zhi-Rong TanDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.
Hong-Hao ZhouDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.
Wei ZhangDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.
Yao ChenDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China. Electronic address: cbohua@csu.edu.cn.
Central South University · CNXiangya Hospital Central South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionPharmacokinetic variability in disease state is common in clinical practice, but its underlying mechanism remains unclear. Recently, gut microbiota has been considered to be pharmacokinetically equivalent to the host liver. Although some studies have explored the roles of gut microbiota and host Cyp450s in drug pharmacokinetics, few have explored their effects on pharmacokinetic variability, especially in disease states.

objectivesIn this study, we aim to investigate the effects of gut microbiota and host Cyp450s on pharmacokinetic variability in mice with non-alcoholic steatohepatitis (NASH), and to elucidate the contribution of gut microbiota and host Cyp450s to pharmacokinetic variability in this setting.

methodsThe pharmacokinetic variability of mice with NASH was explored under intragastric and intravenous administrations of a cocktail mixture of omeprazole, phenacetin, midazolam, tolbutamide, chlorzoxazone, and metoprolol, after which the results were compared with those obtained from the control group. Thereafter, the pharmacokinetic variabilities of all drugs and their relations to the changes in gut microbiota and host Cyp450s were compared and analyzed.

resultsThe exposures of all drugs, except metoprolol, significantly increased in the NASH group under intragastric administration. However, no significant increase in the exposure of all drugs, except tolbutamide, was observed in the NASH group under intravenous administration. The pharmacokinetic variabilities of phenacetin, midazolam, omeprazole, and chlorzoxazone were mainly associated with decreased elimination activity in the gut microbiota. By contrast, the pharmacokinetic variability of tolbutamide was mainly related to the change in the host Cyp2c65. Notably, gut microbiota and host Cyp450s exerted minimal effects on the pharmacokinetic variability of metoprolol.

conclusionGut microbiota and host Cyp450s co-contribute to the pharmacokinetic variability in mice with NASH, and the degree of contribution varies from drug to drug. The present findings provide new insights into the explanation of pharmacokinetic variability in disease states.

Indexed as

Gastrointestinal MicrobiomeNon-alcoholic Fatty Liver DiseaseAnimalsChlorzoxazoneMetoprololMiceMidazolamOmeprazolePharmaceutical PreparationsPhenacetinTolbutamideChlorzoxazoneMetoprololMidazolamOmeprazolePharmaceutical PreparationsPhenacetinTolbutamideGut microbiotaHost Cyp450sNon-alcoholic steatohepatitisPersonalized medicinePharmacokinetic variability

Identifiers

PMID35777915
PMCPMC9263650
OpenAlexW3214388489

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.