Evidence map›Paper›PMID 32216086›Full record

Observational studyClinical and translational science2020

Enhanced Characterization of Drug Metabolism and the Influence of the Intestinal Microbiome: A Pharmacokinetic, Microbiome, and Untargeted Metabolomics Study.

Alan K Jarmusch, Alison Vrbanac, Jeremiah D Momper, Joseph D Ma, Maher Alhaja, Marlon Liyanage, Rob Knight, Pieter C Dorrestein, Shirley M Tsunoda

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in Clinical and translational science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 15% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. DInternational journal of molecular sciences · 2026
    Article
  4. Review
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  6. Review
  7. Article
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  11. Review
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  16. Recent advances in the ontogeny of drug disposition.British journal of clinical pharmacology · 2022
    Review
  17. Article
  18. Physicochemical properties determining drug detection in skin.Clinical and translational science · 2022
    Article
  19. Review
  20. Article
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

9 authors at 2 institutions in 1 country.

Alan K JarmuschSkaggs School of Pharmacy and Pharmaceutical Sciences and Collaborative Mass Spectrometry Innovation Center, University of California, San Diego, La Jolla, California, USA.
Alison VrbanacDepartment of Pediatrics, University of California, San Diego, La Jolla, California, USA.
Jeremiah D MomperSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA.
Joseph D MaSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA.
Maher AlhajaSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA.
Marlon LiyanageSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA.
Rob KnightDepartment of Pediatrics, University of California, San Diego, La Jolla, California, USA.
Pieter C DorresteinSkaggs School of Pharmacy and Pharmaceutical Sciences and Collaborative Mass Spectrometry Innovation Center, University of California, San Diego, La Jolla, California, USA.
Shirley M TsunodaSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA.
University of California, San Diego · USUniversity of Montana · US

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
Systems Biology Approach to Redefine Susceptibility Testing and Treatment of MDR Pathogens in the Context of Host ImmunityU01AI124316 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PALSSON, BERNHARD O · 2016 to 2020
$10.2M
TrainingP41GM103484 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PEVZNER, PAVEL A · 2012 to 2018
$8.7M
Synapt ion mobility mass spectrometerS10RR029121 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DORRESTEIN, PIETER C · 2011 to 2011
$802k
NCATS NIH HHS UL1 TR001442NCRR NIH HHS S10 RR029121NIAID NIH HHS U01 AI124316NIGMS NIH HHS P41 GM103484
6 · The paper itself

Abstract

Determining factors that contribute to interindividual and intra-individual variability in pharmacokinetics (PKs) and drug metabolism is essential for the optimal use of drugs in humans. Intestinal microbes are important contributors to variability; however, such gut microbe-drug interactions and the clinical significance of these interactions are still being elucidated. Traditional PKs can be complemented by untargeted mass spectrometry coupled with molecular networking to study the intricacies of drug metabolism. To show the utility of molecular networking on metabolism we investigated the impact of a 7-day course of cefprozil on cytochrome P450 (CYP) activity using a modified Cooperstown cocktail and assessed plasma, urine, and fecal data by targeted and untargeted metabolomics and molecular networking in healthy volunteers. This prospective study revealed that cefprozil decreased the activities of CYP1A2, CYP2C19, and CYP3A, decreased alpha diversity and increased interindividual microbiome variability. We further demonstrate a relationship between the loss of microbiome alpha diversity caused by cefprozil and increased drug and metabolite formation in fecal samples. Untargeted metabolomics/molecular networking revealed several omeprazole metabolites that we hypothesize may be metabolized by both CYP2C19 and bacteria from the gut microbiome. Our observations are consistent with the hypothesis that factors that perturb the gut microbiome, such as antibiotics, alter drug metabolism and ultimately drug efficacy and toxicity but that these effects are most strongly revealed on a per individual basis.

Indexed as

AdultAgedAnti-Bacterial AgentsCefprozilCephalosporinsCross-Over StudiesCytochrome P-450 CYP1A2Cytochrome P-450 CYP2C19Cytochrome P-450 CYP3ADrug InteractionsFecesFemaleGastrointestinal MicrobiomeHealthy VolunteersHumansMaleAnti-Bacterial AgentsCefprozilCephalosporinsCYP1A2 protein, humanCYP2C19 protein, humanCYP3A protein, humanCytochrome P-450 CYP1A2Cytochrome P-450 CYP2C19Cytochrome P-450 CYP3AOmeprazole

Identifiers

PMID32216086
PMCPMC7485946
OpenAlexW3013588846

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.