A water-soluble preparation for intravenous administration of isorhamnetin and its pharmacokinetics in rats.
Chem Biol Interact
; 396: 111064, 2024 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-38768772
ABSTRACT
Flavonoids are considered as health-protecting food constituents. The testing of their biological effects is however hampered by their low oral absorption and complex metabolism. In order to investigate the direct effect(s) of unmetabolized flavonoid, a preparation in a biologically friendly solvent for intravenous administration is needed. Isorhamnetin, a natural flavonoid and a human metabolite of the most frequently tested flavonoid quercetin, has very low water solubility (<3.5 µg/mL). The aim of this study was to improve its solubility to enable intravenous administration and to test its pharmacokinetics in an animal model. By using polyvinylpyrrolidone (PVP10) and benzalkonium chloride, we were able to improve the solubility approximately 600 times to 2.1 mg/mL. This solution was then administered intravenously at a dose of 0.5 mg/kg of isorhamnetin to rats and its pharmacokinetics was analyzed. The pharmacokinetics of isorhamnetin corresponded to two compartmental model with a rapid initial distribution phase (t1/2α 5.7 ± 4.3 min) and a slower elimination phase (t1/2ß 61 ± 47.5 min). Two sulfate metabolites were also identified. PVP10 and benzalkonium did not modify the properties of isorhamnetin (iron chelation and reduction, and cell penetration) substantially. In conclusion, the novel preparation reported in this study is suitable for future testing of isorhamnetin effects under in vivo conditions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quercetina
/
Solubilidad
/
Agua
/
Povidona
/
Administración Intravenosa
Límite:
Animals
Idioma:
En
Revista:
Chem Biol Interact
Año:
2024
Tipo del documento:
Article
Pais de publicación:
IE
/
IRELAND
/
IRLANDA