Effect of ABCB1 most frequent polymorphisms on the accumulation of bictegravir in recombinant HEK293 cell lines.
Integrase strand transfer inhibitors
MDR1
Multi-drug resistance protein 1
P-glycoprotein
P-gp
Pharmacogenetic
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
15 Jul 2024
15 Jul 2024
Historique:
received:
12
02
2024
accepted:
04
07
2024
medline:
16
7
2024
pubmed:
16
7
2024
entrez:
15
7
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39009738
doi: 10.1038/s41598-024-66809-0
pii: 10.1038/s41598-024-66809-0
doi:
Substances chimiques
ABCB1 protein, human
0
ATP Binding Cassette Transporter, Subfamily B
0
bictegravir
8GB79LOJ07
Piperazines
0
Heterocyclic Compounds, 3-Ring
0
Amides
0
Pyridones
0
Heterocyclic Compounds, 4 or More Rings
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
16290Subventions
Organisme : Fonds De La Recherche Scientifique - FNRS
ID : FNRS-CDR J.0085.21
Informations de copyright
© 2024. The Author(s).
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