Evidence map›Paper›PMID 25802327›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2015

Prediction of gestational age-dependent induction of in vivo hepatic CYP3A activity based on HepaRG cells and human hepatocytes.

Zufei Zhang, Muhammad Farooq, Bhagwat Prasad, Sue Grepper, Jashvant D Unadkat

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

Article in Drug metabolism and disposition: the biological fate of chemicals, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.3field-weighted citation impact, top 17% 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, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Impact of sex and pregnancy on hepatic CYP3A4 expression and activity in a humanized mouse model.Drug metabolism and disposition: the biological fate of chemicals · 2025
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  14. Development and Verification of a LinkedDrug metabolism and disposition: the biological fate of chemicals · 2021
    Article
  15. Article
  16. Prediction of Drug Clearance from Enzyme and Transporter Kinetics.Methods in molecular biology (Clifton, N.J.) · 2021
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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

5 authors at 2 institutions in 2 countries.

Zufei ZhangDepartment of Pharmaceutics, University of Washington, Seattle, Washington (Z.Z., M.F., B.P., J.D.U.); and Life Technologies, Carlsbad, California (S.G.).
Muhammad FarooqDepartment of Pharmaceutics, University of Washington, Seattle, Washington (Z.Z., M.F., B.P., J.D.U.); and Life Technologies, Carlsbad, California (S.G.).
Bhagwat PrasadDepartment of Pharmaceutics, University of Washington, Seattle, Washington (Z.Z., M.F., B.P., J.D.U.); and Life Technologies, Carlsbad, California (S.G.).
Sue GrepperDepartment of Pharmaceutics, University of Washington, Seattle, Washington (Z.Z., M.F., B.P., J.D.U.); and Life Technologies, Carlsbad, California (S.G.).
Jashvant D UnadkatDepartment of Pharmaceutics, University of Washington, Seattle, Washington (Z.Z., M.F., B.P., J.D.U.); and Life Technologies, Carlsbad, California (S.G.) jash@u.washington.edu.
Thermo Fisher Scientific (Norway) · NOUniversity of Washington · US

Funding

Understanding Fetal Exposure to Cannabinoids Through In Vitro and In Vivo StudiesP01DA032507 · NIDA · UNIVERSITY OF WASHINGTON · PI UNADKAT, JASHVANT D · 2013 to 2023
$12.4M
NIDA NIH HHS P01 DA032507NIDA NIH HHS P01DA032507
6 · The paper itself

Abstract

In pregnant women, CYP3A activity increases by 100% during the third trimester (T3). Due to logistical and ethical constraints, little is known about the magnitude of CYP3A induction during the first trimester (T1) and second trimester (T2). Our laboratory has shown that sandwich-cultured human hepatocytes (SCHH) and HepaRG cells have the potential to predict the magnitude of in vivo induction of CYP3A activity likely to be observed in T1 and T2. Therefore, we incubated SCHH and HepaRG cells with plasma concentrations of various pregnancy-related hormones (PRHs)-individually or in combination-observed during T1, T2, or T3 in pregnant women. Then, CYP3A activity was measured by 1'-OH-midazolam formation. In all three trimesters, only cortisol (C) consistently and significantly induced CYP3A activity, while other individual hormones (progesterone, estradiol, or growth hormones) failed to induce CYP3A activity. At physiologically relevant 1× plasma concentrations, the magnitude of CYP3A induction by C or the combination of all PRHs did not change significantly with gestational age. The pattern of induction of CYP3A activity in SCHH by the hormones was similar to that in HepaRG cells. Based on these data, we conclude that C remains the major inducer of CYP3A activity earlier in gestation. Moreover, we predict that the magnitude of CYP3A induction during T1 and T2 will be similar to that observed during T3 (∼100% increase versus postpartum). This prediction is consistent with the observation of similar increases in T2 and T3 oral clearance of indinavir (a CYP3A cleared drug) versus postpartum.

Indexed as

Enzyme InductionModels, BiologicalAdolescentAdultCell LineCells, CulturedCytochrome P-450 CYP3AEstradiolFemaleHepatocytesHuman Growth HormoneHumansHydrocortisoneOsmolar ConcentrationPregnancyPregnancy Trimester, FirstCYP3A protein, humanCytochrome P-450 CYP3AEstradiolHuman Growth HormoneHydrocortisoneProgesterone

Identifiers

PMID25802327
PMCPMC4429679
OpenAlexW2169838987

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.