Effects of drug transporters on the intestinal absorption of trans-resveratrol

Aim: To conduct in vivo and in vitro investigations of the effects of bromosulfophthalein (BSP) on trans-resveratrol (TR) absorption, and to study the possible role of drug transporters in TR intestinal absorption. Methods: TR intestinal absorption and absorption regions were studied by using everted gut sacs, and the influence of Mrp-2 and P-glycoprotein (P-gp) inhibitors on TP absorption was evaluated in everted gut sac. In addition, the effect of BSP on TR pharmacokinetics in intact rats by oral administration and tail vein injection was studied. Results: Application of the everted gut sac showed that TR was well absorbed from the intestinal segments tested (P_app > 1 × 10-⁶ cm/s), and it seemed that TR has marked permeability coefficient in rat ileum. Both Mrp-2 inhibitors such as probenecid and nonP-gp inhibitors such as BSP significantly increased TR absorption in the ileum. But no effect was observed in the presence of digoxin and verapamil. In comparison to tail vein injection, oral coadministration of TR with BSP resulted in significant increases in c_max and bioavailability. Conclusion: It is proved that Mrp-2 is involved in the TR absorption and that inhibition of Mrp-2 can significantly increase TR absorption and bioavailability in the model via oral route.