Uptake and transport characteristics of metformin in Caco-2 cell line

Aim To investigate the uptake,permeability and transport characteristics of metformin in Caco-2 cells at both cellular and molecular levels and the interaction with the multidrug resistance-associatedpro-teins,especially P-glycoprotein.Methods The uptake and permeability of metformin in Caco-2 cells were measured using HPLC;The effect of metformin on MDR1 mRNA expression was determined by RT-PCR;A calcein AM assay was used to evaluate the interaction between metformin and P-glycoprotein (P-gp) and multidrug resistance-associated proteins (MRP1 and MRP2).Results Metformin was readily absorbed in a concentration-related manner and easily permeated in Caco-2 cells (Papp2.86×10-6cm·s-1). Co-incubation with verapamil did not alter the uptake and permeability of metformin.The expression of MDR1 in the cells was up-regulated by metformin,whereas it had no affect on calcein levels in Caco-2 cells.Conclusions Metformin is well-permeable cross Caco-2 monolayers.The drug isn't a P-gp substrate,and has a role in up-regulation of MDR1 expression.Metformin has no inhibitory effect on overall functions of P-pg and MRPs.