Transport characteristics of Candesartan and Candesartan cilexetil in Caco-2 cell model

OBJECTIVE To study on the transport characteristics of Candesartan and Candesartan cilexetil in Caco-2 cell monolayers.METHODS Caco-2 cell model in vitro was applied to study the transport characteristics of Candesartan and Candesartan cilexetil. The effects of concentration,pH and P-glycoprotein (P-gp) inhibitor verapamil on the transport of Candesartan and Candesartan cilexetil were investigated.RESULTS In the Caco-2 monolayers,the absorptive transport of candesartan and candesartan cilexetil was pH dependent,while the secretive transport of both drugs was concentration dependent. The comparison of apical to basolateral(AP-BL) and basolateral to apical( BL-AP) transports showed that efflux effects limited the oral absorption of Candesartan and Candesartan cilexetil and Candesartan cilexetil had a higher Papp,ba.In the presence of Verapamil (10,100 μmol·L-1),a potent inhibitor of P-gp,the efflux value of Candesartan and Candesartan cilexetil decreased significantly (P0.01).CONCLUSION The results showed that Candesartan cilexetil was superior to Candesartan in the transepithelial transport and the polarized efflux of Candesartan and Candesartan cilexetil in Caco-2 monolayers is probably due to the presence of efflux transport protein such as P-gp.