Evidence map›Paper›PMID 39009738›Full record

ArticleScientific reports2024

Effect of ABCB1 most frequent polymorphisms on the accumulation of bictegravir in recombinant HEK293 cell lines.

Julien De Greef, Mathilde Akue, Nadtha Panin, Kévin-Alexandre Delongie, Marina André, Gwenaëlle Mahieu, Emilia Hoste, Laure Elens, Leïla Belkhir, Vincent Haufroid

Abstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Review
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

10 authors.

Julien De GreefLouvain Centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium. julien.degreef@saintluc.uclouvain.be.
Mathilde AkueLouvain Centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Nadtha PaninLouvain Centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Kévin-Alexandre DelongieDepartment of Clinical Chemistry, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Marina AndréLouvain Centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Gwenaëlle MahieuIntegrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Emilia HosteIntegrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics, Louvain Drug Research Institute, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Laure ElensLouvain Centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Leïla Belkhir *Louvain Centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium.
Vincent Haufroid *Louvain Centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain (UCLouvain), Brussels, Belgium.

Funding

Fonds De La Recherche Scientifique - FNRS FNRS-CDR J.0085.21
6 · The paper itself

Abstract

Bictegravir, a key second-generation integrase strand transfer inhibitor in the treatment of HIV, is subject to active efflux transport mediated by ABCB1 (P-glycoprotein). Several coding variants of ABCB1 have been described and associated with variable effects on substrate drugs pharmacokinetics. Here, we investigated the effect of the four most common coding ABCB1 single nucleotide polymorphisms (i.e., c.1199G > A, c.1236C > T, c.2677G > T and c.3435C > T) on the intracellular accumulation of bictegravir. Using a previously validated HEK293 recombinant cell line model, we found decreased bictegravir intracellular concentrations in cell lines overexpressing ABCB1 as compared to control cell lines, in line with the known role of ABCB1 in bictegravir transport. However, we were unable to demonstrate any significant difference in bictegravir intracellular accumulation when comparing HEK293 cells overexpressing the wild type (1236C-2677G-3435C, 1199G) or the variant (1236C-2677G-3435T, 1236T-2677T-3435T or 1199A) proteins. These findings suggest that the ABCB1 c.1199G > A and c.1236C > T-c.2677G > T-c.3435C > T variants have no or at least limited impact on the active transport of bictegravir by ABCB1.

Indexed as

ATP Binding Cassette Transporter, Subfamily BPiperazinesPolymorphism, Single NucleotideAmidesHEK293 CellsHeterocyclic Compounds, 3-RingHeterocyclic Compounds, 4 or More RingsHumansPyridonesABCB1 protein, humanAmidesATP Binding Cassette Transporter, Subfamily BbictegravirHeterocyclic Compounds, 3-RingHeterocyclic Compounds, 4 or More RingsPiperazinesPyridonesIntegrase strand transfer inhibitorsMDR1Multi-drug resistance protein 1P-glycoproteinP-gpPharmacogenetic

Identifiers

PMID39009738
PMCPMC11251168

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.