Transepithelial transport of bepridil in the human intestinal cell line, Caco-2, using a “dynamic model”

The purpose of the study was to go further into the transepithetial transport of bepridil, an anticalcic agent, through monolayer cells Caco-2, using a “dynamic model” including a transfer of inserts with Caco-2 cells into new wells, free of drug, at regular intervals, in order to simulate the blood flux. The state of cells was evaluated by measuring the transepithelial electrical resistance and the transport of bepridil was followed using a gas chromatography/mass spectrometry determination. This study exhibits the importance of the basolateral renewal both on the trasport of bepridil and the maintenance of cells in a satisfactory state. Two elimination phases from the cell compartment seem to occur, with basolateral half lives respectively of 12.2 and 25.6 hours, probably linked with two kinds of cellular binding sites. This dynamic model permits the reflection and simulation of the slowness of the in vivo absorption of bepridil in the small intestine.