6-Methylcoumarin (Toncarine) (6MC) is a semisynthetic coumarin with important in vitro and in vivo anti-inflammatory activity.

Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. suggested that 6MC could be transported across the gut wall by passive diffusion

6-Methylcoumarin(6MC) could be transported across the gut wall by passive diffusion. 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. 6MC has high accumulation in the liver, and widespread distribution in all the organs evaluated.

The determination of in vitro intestinal permeability of 6MC was carried out under sink conditions in a series of pH-gradient bidirectional transport experiments with Caco-2 cells. Before the experiments, cell monolayers were rinsed with Hank's balanced salt solution (HBSS) and equilibrated for 30 min at 37 °C. The integrity of the monolayers was assessed before and after the experiments, by transepithelial electrical resistance (TEER) measurement. Only monolayers with TEER values above 200 Ωcm2 were considered. A stock solution of 6MC (10 mM DMSO) was diluted to final concentration of 10, 25, 50 or 100 μM in HBSS pH 6.5 (apical transport buffer) or pH 7.4 (basolateral transport buffer). Bidirectional experiments (apical-to-basolateral [AB] and basolateral-to-apical [BA]) were initiated by adding 6MC solutions to the donor compartment, and fresh buffer to the acceptor compartment. Caco-2 cell monolayers were incubated for 1 h at 37 °C under constant stirring (150 rpm). Receiver compartments were sampled at 0, 15, 30, 45 and 60 min, refilled with an equivalent amount of transport buffer, and samples were submitted to analysis by HPLC/UV.