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Effects of citicholine and dimethylsulfoxide on transepithelial transport of passively diffused drugs in the Caco-2 cell culture model.
International Journal of Pharmaceutics 2003 January 31
The objective of this study was to determine, using a Caco-2 cell monolayer model, the extent to which the paracellular and transcellular routes are altered by citicholine (CDP-Ch) and DMSO in the presence of human serum albumin (HSA). The apparent permeability (Papp) of mannitol in the presence of 4% (w/v) HSA was investigated using 0, 0.5, 1.0, 2.5, 5.0, and 10.0% (v/v)) of DMSO. The Papp for mannitol ranged from 0.56 x 10(-6) to 0.89 x 10(-6) cm/s (mean 0.77 x 10(-6)). Increasing the concentration of DMSO does not appear to have an effect on the paracellular transport of mannitol and on the transepithelial resistance (TEER) of the monolayer, (P>0.05). The effect of citicholine (CDP-Ch) was investigated in confluent Caco-2 cell monolayers incubated in the presence of 2, 4, 10, 40, 60, 100 and 200 mM CDP-Ch at 37 degrees C in an atmosphere of 7% CO(2) and 95% relative humidity. Papp of mannitol and diltiazem in the presence of CDP-Ch ranged from 0.53 x 10(-6) to 8.52 x 10(-6) cm/s and from 1.30 x 10(-5) to 2.71 x 10(-5) cm/s, respectively. CDP-Ch may have an effect on the stability of the tight junction complex resulting in an increase in the apparent permeability of mannitol.
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