Evidence for a polarized efflux system in Caco-2 cells capable of modulating cyclosporin A transport
Augustijns, Patrick × Bradshaw, Timothy P. Gan, Liang-Shang L. Hendren, R. Wayne Thakker, Dhiren #
Biochemical and Biophysical Research Communications vol:197 issue:2 pages:360-365
The characteristics of cyclosporin A (CsA) transport across Caco-2 monolayers were investigated. CsA (0.25-5.0 mu-M) was transported in a time and concentration dependent manner. The total amount of apical (AP) to basolateral (BL) transport was non-linearly related to CsA concentration from 0.25 to 1 mu-M and was linear from about 1 to 5 mu-M. Average permeability coefficient (P-app) values obtained in the AP to BL direction showed CsA concentration (0.5 and 5.0 mu-M) dependence, whereas those of the reverse (BL to AP) process did not. Papp values for the AP to BL direction were also markedly lower. When the P-glycoprotein pump inhibitors, chlorpromazine and progesterone, were included in the transport medium we observed a significant increase in CsA (0.5 This study suggests that CsA is transported across Caco-2 cells by passive diffusion, but that a and 5.0 mu-M) transport from the AP to BL direction; transport was decreased in the reverse direction.