Exploring the effect of Wuzhi capsule on the pharmacokinetics of regorafenib and its main metabolites in rat plasma using liquid chromatography-tandem mass spectrometry.
J Sep Sci
; 47(5): e2300923, 2024 Mar.
Article
en En
| MEDLINE
| ID: mdl-38466147
ABSTRACT
Regorafenib is a small-molecule tyrosine kinase inhibitor with severe hepatotoxicity. It undergoes metabolism mainly by CYP3A4 to generate active metabolites regorafenib-N-oxide (M2) and N-desmethyl-regorafenib-N-oxide (M5). Wuzhi capsule (WZC) is an herbal preparation derived from Schisandra sphenanthera and is potentially used to prevent regorafenib-induced hepatotoxicity. This study aims to explore the effect of WZC on the pharmacokinetics of regorafenib in rats. An efficient and sensitive liquid chromatography-tandem mass spectrometry method was developed to quantitatively determine regorafenib and its main metabolites in rat plasma. The proposed method was applied to the pharmacokinetic study of regorafenib in rats, with or without WZC. Coadministration of regorafenib with WZC resulted in a prolonged mean residence time (MRT) of the parent drug but had no statistically significant difference in other pharmacokinetic parameters. While for the main metabolites of regorafenib, WZC decreased the area under the curve and maximum concentration (Cmax ), delayed the time to reach Cmax , and prolonged the MRT of M2 and M5. These results indicate that WZC delayed and inhibited the metabolism of regorafenib to M2 and M5 by suppressing CYP3A4. Our study provides implications for the rational use of the WZC-regorafenib combination in clinical practice.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Compuestos de Fenilurea
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Piridinas
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Medicamentos Herbarios Chinos
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Citocromo P-450 CYP3A
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Enfermedad Hepática Inducida por Sustancias y Drogas
Límite:
Animals
Idioma:
En
Revista:
J Sep Sci
Año:
2024
Tipo del documento:
Article
País de afiliación:
China