Evidence map›Paper›PMID 32193355›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2020

Hepatic Transcript Profiles of Cytochrome P450 Genes Predict Sex Differences in Drug Metabolism.

James C Fuscoe, Vikrant Vijay, Joseph P Hanig, Tao Han, Lijun Ren, James J Greenhaw, Richard D Beger, Lisa M Pence, Qiang Shi

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

Article in Drug metabolism and disposition: the biological fate of chemicals, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

12 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
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  3. Hallmarks of Cancer Cachexia: Sexual Dimorphism in Related Pathways.International journal of molecular sciences · 2025
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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

9 authors at 2 institutions in 1 country.

James C FuscoeDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas (J.C.F., V.V., T.H., L.R., J.J.G., R.D.B., L.M.P., Q.S.); and Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland (J.P.H.) jfuscoe@gmail.com.
Vikrant VijayDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas (J.C.F., V.V., T.H., L.R., J.J.G., R.D.B., L.M.P., Q.S.); and Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland (J.P.H.) vikrant.vijay@fda.hhs.gov.
Joseph P HanigDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas (J.C.F., V.V., T.H., L.R., J.J.G., R.D.B., L.M.P., Q.S.); and Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland (J.P.H.).
Tao HanDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas (J.C.F., V.V., T.H., L.R., J.J.G., R.D.B., L.M.P., Q.S.); and Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland (J.P.H.).
Lijun RenDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas (J.C.F., V.V., T.H., L.R., J.J.G., R.D.B., L.M.P., Q.S.); and Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland (J.P.H.).
James J GreenhawDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas (J.C.F., V.V., T.H., L.R., J.J.G., R.D.B., L.M.P., Q.S.); and Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland (J.P.H.).
Richard D BegerDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas (J.C.F., V.V., T.H., L.R., J.J.G., R.D.B., L.M.P., Q.S.); and Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland (J.P.H.).
Lisa M PenceDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas (J.C.F., V.V., T.H., L.R., J.J.G., R.D.B., L.M.P., Q.S.); and Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland (J.P.H.).
Qiang ShiDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas (J.C.F., V.V., T.H., L.R., J.J.G., R.D.B., L.M.P., Q.S.); and Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland (J.P.H.).
United States Food and Drug Administration · USCenter for Drug Evaluation and Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Safety assessments of new drug candidates are an important part of the drug development and approval process. Often, possible sex-associated susceptibilities are not adequately addressed, and better assessment tools are needed. We hypothesized that hepatic transcript profiles of cytochrome P450 (P450) enzymes can be used to predict sex-associated differences in drug metabolism and possible adverse events. Comprehensive hepatic transcript profiles were generated for F344 rats of both sexes at nine ages, from 2 weeks (preweaning) to 104 weeks (elderly). Large differences in the transcript profiles of 29 drug metabolizing enzymes and transporters were found between adult males and females (8-52 weeks). Using the PharmaPendium data base, 41 drugs were found to be metabolized by one or two P450 enzymes encoded by sexually dimorphic mRNAs and thus were candidates for evaluation of possible sexually dimorphic metabolism and/or toxicities. Suspension cultures of primary hepatocytes from three male and three female adult rats (10-13 weeks old) were used to evaluate the metabolism of 11 drugs predicted to have sexually dimorphic metabolism. The pharmacokinetics of the drug or its metabolite was analyzed by liquid chromatography/tandem mass spectrometry using multiple reaction monitoring. Of those drugs with adequate metabolism, the predicted significant sex-different metabolism was found for six of seven drugs, with half-lives 37%-400% longer in female hepatocytes than in male hepatocytes. Thus, in this rat model, transcript profiles may allow identification of potential sex-related differences in drug metabolism. SIGNIFICANCE STATEMENT: The present study showed that sex-different expression of genes coding for drug metabolizing enzymes, specifically cytochrome P450s, could be used to predict sex-different drug metabolism and, thus, provide a new tool for protecting susceptible subpopulations from possible adverse drug events.

Indexed as

Gene Expression Regulation, EnzymologicAnimalsCells, CulturedCytochrome P-450 Enzyme SystemDatasets as TopicFemaleGene Expression ProfilingHalf-LifeHepatocytesLiverMaleMetabolic Clearance RateModels, AnimalPrimary Cell CultureRatsRats, Inbred F344Cytochrome P-450 Enzyme System

Identifiers

PMID32193355
PMCPMC7250365
OpenAlexW3012400425

What OpenQuestion holds

Textmetadata
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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.