Evidence map›Paper›PMID 28260174›Full record

ArticleEuropean journal of drug metabolism and pharmacokinetics2017

Effect of Gevokizumab on Interleukin-1β-Mediated Cytochrome P450 3A4 and Drug Transporter Repression in Cultured Human Hepatocytes.

Amélie Moreau, Marc Le Vée, Elodie Jouan, Claire Denizot, Yannick Parmentier, Olivier Fardel

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Article in European journal of drug metabolism and pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 38% 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

3 citing papers in PubMed, 9 citations in OpenAlex.

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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

6 authors at 3 institutions in 1 country.

Amélie MoreauCentre de Recherche en Pharmacocinétique, Technologie Servier, Orléans, France.
Marc Le VéeInstitut de Recherches en Santé, Environnement et Travail (IRSET) UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 34043, Rennes, France.
Elodie JouanInstitut de Recherches en Santé, Environnement et Travail (IRSET) UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 34043, Rennes, France.
Claire DenizotCentre de Recherche en Pharmacocinétique, Technologie Servier, Orléans, France.
Yannick ParmentierCentre de Recherche en Pharmacocinétique, Technologie Servier, Orléans, France.
Olivier FardelInstitut de Recherches en Santé, Environnement et Travail (IRSET) UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 34043, Rennes, France. olivier.fardel@univ-rennes1.fr.
Centre de Biophysique Moléculaire · FRInstitut de Recherche en Santé, Environnement et Travail · FRInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesGevokizumab is a potent anti-interleukin (IL)-1β neutralizing monoclonal antibody (mAb), which may be used for treating inflammatory or autoimmune diseases. The present study was designed to characterize the potential effects of this mAb towards well-established IL-1β-mediated repression of hepatic drug detoxifying proteins, like cytochrome P450 (CYP) 3A4 and drug transporters.

methodsPrimary cultured human hepatocytes were exposed to various concentrations of IL-1β in the absence or presence of gevokizumab (5 µg/mL); mRNA expression and activity of CYP3A4 and transporters were next determined.

resultsGevokizumab was found to down-modulate, but not abolish, the repression of CYP3A4 and drug transporter mRNAs caused by IL-1β in human hepatocytes, through shifting up IL-1β half maximal inhibitory concentration (IC

conclusionGevokizumab attenuates, but not abolishes, IL-1β-mediated functional repression of CYP3A4 and drug transporters in human hepatocytes, which agrees with the fact that the mAb is considered as a modulator and not a blocker of IL-1β signaling. This attenuation of IL-1β-mediated down-regulation of hepatic detoxifying proteins by gevokizumab may have to be evaluated in terms of potential therapeutic protein drug-drug interactions when considering future development and therapeutic uses of this IL-1β neutralizing mAb.

Indexed as

AgedAntibodies, Monoclonal, HumanizedBiological TransportCell LineCytochrome P-450 CYP3ADrug InteractionsFemaleHepatocytesHumansInterleukin-1betaMiddle AgedOrganic Anion TransportersAntibodies, Monoclonal, HumanizedCYP3A4 protein, humanCytochrome P-450 CYP3AgevokizumabInterleukin-1betaOrganic Anion TransportersDenosumabDrug TransporterHuman HepatocyteProbenecidTocilizumab

Identifiers

PMID28260174
OpenAlexW2592106156

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.