Evidence map›Paper›PMID 28986475›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2017

Pediatric Cytochrome P450 Activity Alterations in Nonalcoholic Steatohepatitis.

Hui Li, Mark J Canet, John D Clarke, Dean Billheimer, Stavra A Xanthakos, Joel E Lavine, Robert P Erickson, Nathan J Cherrington

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

15 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Development of anFrontiers in pharmacology · 2025
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  14. Alcohol Metabolism in the Progression of Human Nonalcoholic Steatohepatitis.Toxicological sciences : an official journal of the Society of Toxicology · 2018
    Article
  15. 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

8 authors at 4 institutions in 1 country.

Hui LiDepartment of Pharmacology and Toxicology (H.L., M.J.C., J.D.C., N.J.C.), Department of Epidemiology and Biostatistics (D.B.), and Department of Pediatrics (R.P.E.), University of Arizona, Tucson, Arizona; Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio (S.A.X.); Columbia University, New York, New York (J.E.L.).
Mark J CanetDepartment of Pharmacology and Toxicology (H.L., M.J.C., J.D.C., N.J.C.), Department of Epidemiology and Biostatistics (D.B.), and Department of Pediatrics (R.P.E.), University of Arizona, Tucson, Arizona; Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio (S.A.X.); Columbia University, New York, New York (J.E.L.).
John D ClarkeDepartment of Pharmacology and Toxicology (H.L., M.J.C., J.D.C., N.J.C.), Department of Epidemiology and Biostatistics (D.B.), and Department of Pediatrics (R.P.E.), University of Arizona, Tucson, Arizona; Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio (S.A.X.); Columbia University, New York, New York (J.E.L.).
Dean BillheimerDepartment of Pharmacology and Toxicology (H.L., M.J.C., J.D.C., N.J.C.), Department of Epidemiology and Biostatistics (D.B.), and Department of Pediatrics (R.P.E.), University of Arizona, Tucson, Arizona; Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio (S.A.X.); Columbia University, New York, New York (J.E.L.).
Stavra A XanthakosDepartment of Pharmacology and Toxicology (H.L., M.J.C., J.D.C., N.J.C.), Department of Epidemiology and Biostatistics (D.B.), and Department of Pediatrics (R.P.E.), University of Arizona, Tucson, Arizona; Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio (S.A.X.); Columbia University, New York, New York (J.E.L.).
Joel E LavineDepartment of Pharmacology and Toxicology (H.L., M.J.C., J.D.C., N.J.C.), Department of Epidemiology and Biostatistics (D.B.), and Department of Pediatrics (R.P.E.), University of Arizona, Tucson, Arizona; Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio (S.A.X.); Columbia University, New York, New York (J.E.L.).
Robert P EricksonDepartment of Pharmacology and Toxicology (H.L., M.J.C., J.D.C., N.J.C.), Department of Epidemiology and Biostatistics (D.B.), and Department of Pediatrics (R.P.E.), University of Arizona, Tucson, Arizona; Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio (S.A.X.); Columbia University, New York, New York (J.E.L.).
Nathan J CherringtonDepartment of Pharmacology and Toxicology (H.L., M.J.C., J.D.C., N.J.C.), Department of Epidemiology and Biostatistics (D.B.), and Department of Pediatrics (R.P.E.), University of Arizona, Tucson, Arizona; Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, Ohio (S.A.X.); Columbia University, New York, New York (J.E.L.) cherrington@pharmacy.arizona.edu.
Cincinnati Children's Hospital Medical Center · USUniversity of Cincinnati · USColumbia University · USUniversity of Arizona · US

Funding

SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
Training in Environmental Toxicology of Human DiseaseT32ES007091 · NIEHS · UNIVERSITY OF ARIZONA · PI Nathan J Cherrington · 1985 to 2026
$10.7M
Pediatric Adverse Drug Reactions in NASHR01HD062489 · NICHD · UNIVERSITY OF ARIZONA · PI CHERRINGTON, NATHAN J · 2011 to 2015
$1.6M
Microcystin-LR toxicity in nonalcoholic steatohepatitisR00ES024455 · NIEHS · WASHINGTON STATE UNIVERSITY · PI CLARKE, JOHN DANIEL · 2017 to 2019
$715k
NCATS NIH HHS UL1 TR000040NICHD NIH HHS R01 HD062489NIDDK NIH HHS P30 DK078392NIEHS NIH HHS P30 ES006694NIEHS NIH HHS R00 ES024455NIEHS NIH HHS T32 ES007091
6 · The paper itself

Abstract

Variable drug responses depend on individual variation in the activity of drug-metabolizing enzymes, including cytochrome P450 enzymes (CYP). As the most common chronic liver disease in children and adults, nonalcoholic steatohepatitis (NASH) has been identified as a source of significant interindividual variation in hepatic drug metabolism. Compared with adults, children present age-related differences in pharmacokinetics and pharmacodynamics. The purpose of this study was to determine the impact of fatty liver disease severity on the activity of a variety of CYP enzymes in children and adolescents. Healthy and nonalcoholic fatty liver disease pediatric subjects aged 12-21 years inclusive received an oral cocktail of four probe drugs: caffeine (CYP1A2, 100 mg), omeprazole (CYP2C19, 20 mg), losartan (CYP2C9, 25 mg), and midazolam (CYP3A4, 2 mg). Venous blood and urine were collected before administration and 1, 2, 4, and 6 hours after administration. Concentrations of the parent drugs and CYP-specific metabolites were quantified in plasma and urine using liquid chromatography with tandem mass spectrometry. In plasma, the decreased metabolic area under the curve (AUC) ratio, defined as the metabolite AUC to parent AUC, of omeprazole indicated significant decreases of CYP2C19 (

Indexed as

AdolescentAdultAgingArea Under CurveChildChromatography, High Pressure LiquidCytochrome P-450 CYP1A2Cytochrome P-450 CYP2C9Cytochrome P-450 Enzyme SystemFemaleGenotypeHumansMaleNon-alcoholic Fatty Liver DiseasePharmaceutical PreparationsYoung AdultCYP1A2 protein, humanCYP2C9 protein, humanCytochrome P-450 CYP1A2Cytochrome P-450 CYP2C9Cytochrome P-450 Enzyme SystemPharmaceutical Preparations

Identifiers

PMID28986475
PMCPMC5697442
OpenAlexW2763644374

What OpenQuestion holds

Textmetadata
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.