Induction effect of antiretroviral bictegravir on the expression of Abcb1, Abcg2 and Abcc1 genes associated with P-gp, BCRP and MRP1 transporters present in rat peripheral blood mononuclear cells.
Expert Opin Drug Metab Toxicol
; 20(6): 529-539, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38712502
ABSTRACT
BACKGROUND:
Antiretrovirals have the potential to cause drug interactions leading to inefficacy or toxicity via induction of efflux transporters through nuclear receptors, altering drug concentrations at their target sites. RESEARCH DESIGN ANDMETHODS:
This study used molecular dynamic simulations and qRT-PCR to investigate bictegravir's interactions with nuclear receptors PXR and CAR, and its effects on efflux transporters (P-gp, BCRP, MRP1) in rat PBMCs. PBMC/plasma drug concentrations were measured using LC-MS/MS to assess the functional impact of transporter expression.RESULTS:
Bictegravir significantly increased the expression of ABC transporters, with Car identified as a key mediator. This suggests that bictegravir's influence on nuclear receptors could affect drug transport and efficacy at the cellular level.CONCLUSIONS:
Bictegravir activates nuclear receptors enhancing efflux transporter expression. Understanding these interactions is crucial for preventing drug-drug interactions and reducing toxicity in clinical use. Combining CAR antagonists with bictegravir may prevent drug resistance and toxicity. However, these findings are based on preclinical data and necessitate further clinical trials to confirm their applicability in clinical settings.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucócitos Mononucleares
/
Interações Medicamentosas
/
Espectrometria de Massas em Tandem
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Compostos Heterocíclicos de 4 ou mais Anéis
Limite:
Animals
Idioma:
En
Revista:
Expert Opin Drug Metab Toxicol
Assunto da revista:
METABOLISMO
/
TOXICOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia
País de publicação:
Reino Unido