Minimal Involvement of P-gp and BCRP in Oral Absorption of Ensitrelvir, An Oral SARS-CoV-2 3C-like Protease Inhibitor, in a Non-Clinical Investigation.
J Pharm Sci
; 113(9): 2871-2878, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38885812
ABSTRACT
P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are important transporters causing drug-drug interaction (DDI). Here, we investigated the involvement of P-gp and BCRP in the oral absorption of ensitrelvir in non-clinical studies and estimated the DDI risk mediated by P-gp and BCRP inhibition in humans. Although ensitrelvir is an in vitro P-gp and BCRP substrate, it demonstrated high bioavailability in rats and monkeys after oral administration. Plasma exposures of ensitrelvir following oral administration were comparable in wild type (WT) and Bcrp (-/-) mice. On the other hand, the area under the plasma concentration-time curve (AUC) ratio of ensitrelvir in the Mdr1a/1b (-/-) mice to the WT mice was 1.92, indicating that P-gp, but not BCRP, was involved in the oral absorption of ensitrelvir. Based on our previous retrospective analyses, such a low AUC ratio (<3) in the Mdr1a/1b (-/-) mice indicates a minimal impact of P-gp on the oral absorption in humans. In conclusion, our studies demonstrate that the involvement of both P-gp and BCRP in the oral absorption of ensitrelvir is minimal, and suggest that ensitrelvir has a low risk for DDIs mediated by P-gp and BCRP inhibition in humans.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ratones Noqueados
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
/
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Pharm Sci
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Estados Unidos