Evidence map›Paper›PMID 33903659›Full record

ArticleScientific reports2021

Effect of four ABCB1 genetic polymorphisms on the accumulation of darunavir in HEK293 recombinant cell lines.

Gabriel Stillemans, Happy Phanio Djokoto, Kévin-Alexandre Delongie, Halima El-Hamdaoui, Nadtha Panin, Vincent Haufroid, Laure Elens

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 47% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. 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

7 authors at 2 institutions in 1 country.

Gabriel StillemansIntegrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.ORCID 0000-0002-2356-4891
Happy Phanio DjokotoIntegrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
Kévin-Alexandre DelongieDepartment of Clinical Chemistry, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Halima El-HamdaouiIntegrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
Nadtha PaninLouvain Centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
Vincent Haufroid *Louvain Centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.ORCID 0000-0001-5040-9806
Laure Elens *Integrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium. laure.elens@uclouvain.be.ORCID 0000-0002-0039-3583
UCLouvain · BECliniques Universitaires Saint-Luc · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The intracellular penetration of darunavir, a second-generation HIV protease inhibitor, is limited by the activity of the efflux P-glycoprotein (ABCB1). ABCB1 expression and/or activity levels can vary between individuals due to genetic polymorphisms including the c.1199G>A, c.1236C>T, c.2677G>T and c.3435C>T variants, which could in part explain why the pharmacokinetics of darunavir are so variable from one individual to another. While a few clinical studies have failed to demonstrate an influence of these polymorphisms on darunavir pharmacokinetics, drug-drug interactions and methodological limitations may have prevented them from revealing the true influence of ABCB1 variants. In this work, we report on the intracellular accumulation of darunavir in recombinant HEK293 cell lines expressing wild-type ABCB1 or one of several variants: ABCB1 1199A, ABCB1 3435T, and ABCB1 1236T/2677T/3435T. We demonstrate that while ABCB1 expression limits intracellular accumulation of darunavir, there is no significant difference in efflux activity between cells expressing wild-type ABCB1 and those that express any of the studied variants.

Indexed as

DarunavirPolymorphism, GeneticATP Binding Cassette Transporter, Subfamily BHEK293 CellsHumansABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BDarunavir

Identifiers

PMID33903659
PMCPMC8076219
OpenAlexW3158710362

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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.