In vitro intestinal permeability studies, pharmacokinetics and tissue distribution of 6-methylcoumarin after oral and intraperitoneal administration in Wistar rats
Braz. J. Pharm. Sci. (Online)
;
53(1): e16081, 2017. tab, graf
Artículo
en Inglés
| LILACS
| ID: biblio-839460
ABSTRACT
ABSTRACT 6-Methylcoumarin (6MC) is a semisynthetic coumarin with important in vitro and in vivo anti-inflammatory activity. In order to continue the pre-clinical characterization of this molecule, in vitro intestinal permeability, plasma profile and tissue distribution after oral administration in rats were studied. The permeability of 6MC was evaluated by the Caco-2 cellular model in both the apical-basal (A-B) and basal-apical (B-A) directions. The pharmacokinetics and biodistribution were evaluated in rats after oral and intraperitoneal administration at doses of 200 mg/kg. Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. This finding suggested that 6MC could be transported across the gut wall by passive diffusion. The plasma concentration-time curve showed that the maximum concentration (Cmax) was 17.13 ± 2.90 µg/mL at maximum time (Tmax) of 30 min for the oral route and Cmax 26.18 ± 2.47 µg/mL at 6.0 min for the intraperitoneal administration, with elimination constant of (Ke ) 0.0070 min-1 and a short life half time of (T1/2 ) lower that 120 min. The distribution study showed that 6MC has high accumulation in the liver, and widespread distribution in all the organs evaluated.
Texto completo:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Permeabilidad
/
Técnicas In Vitro
/
Administración Oral
/
Ratas Wistar
/
Cumarinas
Tipo de estudio:
Estudio pronóstico
Límite:
Animales
Idioma:
Inglés
Revista:
Braz. J. Pharm. Sci. (Online)
Asunto de la revista:
Farmacologia
/
Teraputica
/
Toxicologia
Año:
2017
Tipo del documento:
Artículo
/
Documento de proyecto
País de afiliación:
Argentina
/
Brasil
/
Colombia
Institución/País de afiliación:
Universidad Nacional de Colombia/CO
/
Universidad Nacional de Córdoba/AR
/
Universidade Federal de Santa Catarina/BR
Similares
MEDLINE
...
LILACS
LIS