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

Authors

  • Paola Andrea Cárdenas Universidad Nacional de Colombia; Departamento de Farmacia; Grupo Sistemas de Liberación Modificada de Moléculas Biológicamente Activas
  • Jadel Müller Kratz Universidade Federal de Santa Catarina; Departamento de Ciências Farmacêuticas; Grupo de Análise e Desenvolvimento de Fármacos de Origem Natural
  • Aura Hernández Universidad Nacional de Colombia; Departamento de Farmacia; Grupo Sistemas de Liberación Modificada de Moléculas Biológicamente Activas
  • Geison Modesti Costa Universidad Nacional de Colombia; Departamento de Química; Grupo de Estudio y Aprovechamiento de Productos Naturales Marinos y Frutas de Colombia
  • Luis Fernando Ospina Universidad Nacional de Colombia; Departamento de Farmacia; Grupo de Principios Bioactivos de Plantas Medicinales
  • Yolima Baena Universidad Nacional de Colombia; Departamento de Farmacia; Grupo Sistemas de Liberación Modificada de Moléculas Biológicamente Activas
  • Cláudia Maria Oliveira Simões Universidade Federal de Santa Catarina; Departamento de Ciências Farmacêuticas; Grupo de Análise e Desenvolvimento de Fármacos de Origem Natural
  • Álvaro Jimenez-Kairuz Universidad Nacional de Córdoba; Facultad de Ciencias Químicas; Departamento de Farmacia
  • Marcela Aragon Universidad Nacional de Colombia; Departamento de Farmacia; Grupo Sistemas de Liberación Modificada de Moléculas Biológicamente Activas

DOI:

https://doi.org/10.1590/s2175-97902017000116081

Keywords:

6-Methylcoumarin/Pharmacokinetics/rats, 6-Methylcoumarin/distribution, Intestinal permeability/study, Intestinal permeability/study/In vitro

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.

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Published

2017-01-01

Issue

Section

Articles

How to Cite

In vitro intestinal permeability studies, pharmacokinetics and tissue distribution of 6-methylcoumarin after oral and intraperitoneal administration in Wistar rats. (2017). Brazilian Journal of Pharmaceutical Sciences, 53(1), e16081-. https://doi.org/10.1590/s2175-97902017000116081