Transport characteristics of rutin deca (H-) sulfonate sodium across Caco-2 cell monolayers

The aim of this study was to explore potential transport mechanisms of rutin deca (H-) sulfonate sodium (RDS) across Caco-2 cell monolayers. As an in-vitro model of human intestinal epithelial membrane, Caco-2 cells were utilized to evaluate the transepithelial transport characteristics of this hydrophilic macromolecular compound. Bi-directional transport study of RIDS demonstrated that the apparent permeability (P-app) in the secretory direction was 1.4 similar to 4.5-fold greater than the corresponding absorptive Papp at concentrations in the range 50.0 similar to 2000 mu m. The transport of RIDS was shown to be concentration, temperature and pH dependent. In the presence of ciclosporin and verapamil, potent inhibitors of P-glycoprotein (P-gp)/MRP2, the absorptive transport was enhanced and secretory efflux was diminished. RIDS significantly reduced the efflux ratio of the P-gp substrate rhodamine-123 in a fashion indicative of P-gp activity suppression, while rhodamine-123 competitively inhibited the polarized transport of the compound. In conclusion, the results indicated that RIDS was likely a substrate of P-gp. Several efflux transporters, including P-gp, participated in the absorption and efflux of RIDS and they might play significant roles in limiting the oral absorption of the compound. These observations offered important information for the pharmacokinetics of RIDS.