Fexofenadine transport in Caco-2 cells: Inhibition with verapamil and ritonavir

This study investigated fexofenadine (FXD) transport and the inhibition of FXD transport in Caco-2 cell monolayer transwells, using rhodamine 123 (1311123) transport as a positive control. FXD transport from the basolateral (B) to apical (A) compartment was fivefold higher than A to B transport. FXD transport was linear with respect to time (up to 270 min) and concentration (up to 300 lam). Similar results were seen with the positive control RH123, Ritonavir (100 W) and verapamil (100 pm) reduced transport of FXD and RH123 by more than 80%, whereas transport was not inhibited by 100 m indomethacin or 2 mM probenecid. This suggests pre-dominantly P-glycoprotein (P-gp)-mediated transport as opposed to transport by multidrug resistance protein. In concentration-response experiments, FXD transport was inhibited by verapamil and ritonavir with IC50 values of 6.5 mum and 5.4 mum, respectively. Results from this in vitro study demonstrate differential transport of FXD across Caco-2 cell monolayers and inhibition of FXD transport by established P-gp inhibitors, The findings support the use of FXD as an index or probe compound to reflect P-gp activity in vivo. (C) 2002 the American College of Clinical Pharmacology.