Effect of resveratrol on the pharmacokinetics of fexofenadine in rats: Involvement of P-glycoprotein inhibition

Resveratrol (RSV) is a natural occurring antioxidant has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro and in vivo, which may have the potential to cause drug–phytochemical interactions. The purpose of the present study was to evaluate the effect of RSV on the pharmacokinetics of fexofenadine (FEX), P-gp substrate in rats. A mechanistic evaluation was undertaken using in vitro non-everted sac and in situ intestinal perfusion studies to determine the FEX intestinal transport and permeability. These results were confirmed by an in vivo pharmacokinetic study of oral administered FEX (10mg/kg) in rats. The intestinal transport and apparent permeability (Papp) of FEX were increased significantly in duodenum, jejunum and ileum of RSV and verapamil (VER) pretreated groups when compared to FEX alone group. Similarly absorption rate constant (Ka), fraction absorbed (Fab) and effective permeability (Peff) of FEX were increased significantly in ileum of RSV and VER pretreated groups when compared to FEX alone group. In comparison with FEX alone, RSV pretreatment significantly increased maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC), while there was no significant change was observed in T1/2 and Tmax of FEX. RSV significantly enhanced the exposure of FEX in rats likely by the inhibition of P-glycoprotein (P-gp) mediated efflux during the intestinal absorption, suggesting that there is a potential pharmacokinetic interaction between RSV and FEX. Therefore, further studies are recommended to evaluate the potential drug–phytochemical interactions in humans.