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
Article
in English
| 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.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Permeability
/
In Vitro Techniques
/
Administration, Oral
/
Rats, Wistar
/
Coumarins
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Braz. J. Pharm. Sci. (Online)
Journal subject:
Farmacologia
/
Teraputica
/
Toxicologia
Year:
2017
Type:
Article
/
Project document
Affiliation country:
Argentina
/
Brazil
/
Colombia
Institution/Affiliation country:
Universidad Nacional de Colombia/CO
/
Universidad Nacional de Córdoba/AR
/
Universidade Federal de Santa Catarina/BR
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