Effect of P-glycoproteinon on the Permeability of Squamosamide Derivative FLZ across Caco-2 monolayer Model

Abstract

Abstract: Objective To study the effect of P-glycoprotein (P-gp) on the transport characteristics of squamosamide derivative FLZ across in vitro blood-brain barrier (BBB) model. Methods A human intestinal epithelial cell Caco-2 in vitro BBB model was applied to study the transport characteristics of 1, 5, 10 μM FLZ．The effects of P-gp inhibitor zosuquidar on the in vitro permeability and efflux ratio of FLZ were also investigated. Results The transport of various concentrations of FLZ (1, 5, 10 μM) through the Caco-2 model occurred in both A~B and B~A directions, and Papp B~A transport were significantly higher than those for A~B transport at each FLZ concentration. The efflux ratio of 1, 5, 10 μM FLZ was 2.56, 3.67 and 5.06, respectively, suggesting the presence of efflux pumps to remove FLZ from within cell membranes. Upon specific blocking of P-gp using zosuquidar increased intracellular accumulation of FLZ in Caco-2 model and significantly reduced the efflux ratio from 5.06 to 1.94. Conclusion FLZ is a substrate for the P-gp drug efflux transporter, and poor brain penetration of FLZ is mainly due to the P-gp transport system in the BBB.

Key words: P-glycoprotein, FLZ, blood-brain barrier, Caco-2

CLC Number:

R965
R971.5

LIU Qian,CHEN Xiao-guang，HOU Jin-feng，ZHANG Jin-lan，CHEN Hui，ZHANG Dan，BAO Xiu-qi，UN Hua. Effect of P-glycoproteinon on the Permeability of Squamosamide Derivative FLZ across Caco-2 monolayer Model[J]. Chinese Journal of Pharmacovigilance, 2015, 12(2): 69-72.

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