Transport Characteristics And The Transport Interaction With Liquiritin Of Brucine Or Hypacontine In Caco-2Cell Monolayer Model

Caco-2cells are from human colon cancer cells, whose structure and function are similar to human intestinal epithelial cells, and contain enzymes related to small intestinal brush border epithelial. Since Caco-2cell monolayer model has a good correlation between the process of drug oral absorption in vitro and the absorption process in the small intestine in vivo, it has been widely used to study drug absorption in vitro, and used to predict drug absorption and absorption interaction in vivo.To study the effects of liquiritin on the transport of brucine and hypacontine in Caco-2cell monolayer model, the transport parameters of brucine and hypacontine, such as apparent permeability coefficient (PappB→A and PappA→B) and the ratio of PappB→A versus PappA→B, were studied and compared when brucine or hypacontine was used solely and co-used with Liquiritin. The effects of drug concentrations, conveying times, P-glyprotein (P-gp) inhibitor verapamil and conveying Liq pH values on the transport of brucine and hypacontine in the conditions above were also investigated.The results indicated that:1.The Papp value of brucine was larger than10-6cm·s-1, and the ratio of Papp B→A versus PappA→B was less than1.5. The absorption of brucine was well and the passive transference was its main intestinal absorption mechanism. The co-treatment of brucine combined with liquiritin increase the ratio of Papp B→versus PappA→B, whereas the co-treatment of brucine combined with verapamil decreased the ratio of Papp B→A versus Papp A→B.Liquiritin and P-glycoprotein inhibited the absorption of brucine,and medium pH had important effect on the transport of brucine.2.The absorption of hypacontine in Caco-2cell monolayer model was well and the passive transference was its main intestinal absorption mechanism.The liquiritin can increase the excretion action of hypacontine mediated by P-gp, and liquiritin had no significant effect on the ratio of PappA→B.The co-treatment of hypacontine combined with liquiritin increase the ratio of PappB→A versus PappA→B, Liquiritin inhibited the absorption of brucine. Meanwhile, medium pH value had significant influence on the transport of hypacontine.