In vitro and in situ effects of atorvastatin and ezetimibe on P-glycoprotein expression and function

P-glycoprotein (P-gp) is a membrane transporter responsible for the active efflux from the cell. Inhibition of the activity may lead to clinically significant drug-drug interactions. This study was performed to investigate the effects of atorvastatin and ezetimibe on the function and expression of P-gp. The in vitro rhodamine-123 (Rho123) efflux assay and Western blot in Caco-2 cells, and the in situ rat single-pass intestinal permeability model followed by high performance liquid chromatography were developed. Rho123 intracellular accumulation in 100 mu M of atorvastatin- and ezetimibe-treated cells was significantly higher than that in control cells (p<0.05). P-gp expression was decreased by 100 mu M atorvastatin and ezetimibe. Intestinal effective permeability of digoxin in the presence of atorvastatin (3 and 100 mu M), ezetimibe (10 and 100 mu M) was significantly increased (p<0.05). Both drugs inhibited P-gp activity in vitro and in situ. Atorvastatin and ezetimibe down-regulated the expression of P-gp in vitro.