In vitro intestinal permeability studies, pharmacokinetics and tissue distribution of 6-methylcoumarin after oral and intraperitoneal administration in Wistar rats

• Autor(a) principal: Cárdenas, Paola Andrea
• Data de Publicação: 2017
• Outros Autores: Kratz, Jadel Müller, Hernández, Aura, Costa, Geison Modesti, Ospina, Luis Fernando, Baena, Yolima, Simões, Cláudia Maria Oliveira, Jimenez-Kairuz, Álvaro, Aragon, Marcela
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Brazilian Journal of Pharmaceutical Sciences
• Texto Completo: https://www.revistas.usp.br/bjps/article/view/131432
• topic: 6-Methylcoumarin/Pharmacokinetics/rats; 6-Methylcoumarin/distribution; Intestinal permeability/study; Intestinal permeability/study/In vitro

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.