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

JIMENEZ KAIRUZ, AF.; OSPINA, LUIS FERNANDO; KRATZ, JADEL MÜLLER; SIMÕES, CLÁUDIA MARIA OLIVEIRA; ARAGON, MARCELA; COSTA, GEISON MODESTI; BAENA, YOLIMA; CÁRDENAS, PAOLA ANDREA; HERNÁNDEZ, AURA

BRAZILIAN JOURNAL OF PHARMACEUTICAL SCIENCES

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas

Lugar: São Paulo; Año: 2017 vol. 53

1984-8250

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, the in vitro intestinal permeability, plasmatic 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 a great distribution in all organs evaluated.