[In vitro metabolism of daphnetin in rat liver S9 fractions].
Yao Xue Xue Bao
; 52(2): 291-5, 2017 Feb.
Article
em Zh
| MEDLINE
| ID: mdl-29979523
ABSTRACT
Daphnetin is quickly eliminated in rats after dosing, but the mechanism remains unclear. This study was aimed to investigate the in vitro metabolism of daphnetin using rat liver S9 fractions (RLS9). The metabolites formed in RLS9 were identified and the kinetic parameters for different metabolic pathways were determined. HPLC-DAD-MS analysis showed that daphnetin was biotransformed to six metabolites, which were identified as 7 or 8 mono-glucuronide and mono-sulfate, 8-methylate, and 7-suflo-8-methylate. Methylation and glucuronidation of daphnetin exhibited the Michaelis-Menten kinetic characteristics, whereas the substrate inhibition kinetic and the two-site kinetic were observed for 8-sulfate and 7-sulfate formations. Of the 3 conjugation pathways, the intrinsic clearance rate for sulfation was highest, followed by methylation and glucuronidation. By in vitro-in vivo extrapolation of the kinetic data measured in RLS9, the hepatic clearance were estimated to be 54.9 mL·min−1·kg−1 which is comparable to the system clearance (58.5 mL·min−1·kg−1) observed in rats. In conclusions, the liver might be the main site for daphnetin metabolism in rats. Sulfation, methylation and glucuronidation are important pathways of the hepatic metabolism of daphnetin in rats.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Umbeliferonas
/
Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
Zh
Revista:
Yao Xue Xue Bao
Ano de publicação:
2017
Tipo de documento:
Article