2010•Zhongguo yaolixue yu dulixue zazhiRequires access
Transport of thiophenorphine across Caco-2 monolayer model
Zheng Li, Xiaomei Zhuang, Suyun Li, Zhenqing Zhang, Ruan Jin-xiu
Open publisher page 2 citations
Abstract
OBJECTIVE To explore the absorption mechanism of thiophenorphine,and its effect on P-glycoprotein(P-gp) expression by using Caco-2 cell monolayer model.METHODSThe LC-MS-MS method was applied to determine thiophenorphine concentration in millicell system.The bi-directional permeability studies were performed to investigate the potential involvement of efflux carriers in the intestinal absorption.P-gp inhibition was studied by flow cytometry using calcein-AM as P-gp substrate.The expression of P-gp was evaluated using Western blotting.RESULTSThiophenorphine transport in Caco-2 cells was in time-dependent manner.Its average apparent permeability coefficient(P_app) was 2.338×10-6 cm·s-1.P_app was increased 2.8 folds by P-gp inhibitor ciclosporin A,and 2.3 folds by mulitdrug resistance-associated protein2(MRP2) inhibitor MK571.The accumulation of calcein-AM and the expression of P-gp in Caco-2 cell line wasn't changed noticeably by thiophenorphine.CONCLUSION Thiophenorphine is a common substrate of P-gp and MRP2 and it shows normal transport in millicell system.The expression of P-gp doesn't induce by thiophenorphine.