Effects of citicholine and dimethylsulfoxide on transepithelial transport of passively diffused drugs in the Caco-2 cell culture model.
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.
Demirbas
Sibel
S
Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, PHR 4.214C, Austin, TX 78712, USA.
Stavchansky
Salomon
S
D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D018938:Caco-2 Cells / Q000187:drug effects / Q000378:metabolism*; D003566:Cytidine Diphosphate Choline / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004058:Diffusion; D004121:Dimethyl Sulfoxide / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D003566:Cytidine Diphosphate Choline; D004121:Dimethyl Sulfoxide