Effect of diosmin on the intestinal absorption and pharmacokinetics of fexofenadine in rats

Background: Diosmin is a natural flavone glycoside, a potent P-glycoprotein (P-gp) inhibitor in cultured cells and have the potential to alter the bioavailability of P-gp substrate drugs. However, the interaction between diosmin and fexofenadine is unreported. Hence, the present study was performed to investigate the effect of diosmin on the intestinal absorption and pharmacokinetics of fexofenadine, a P-gp substrate in rats. Methods: Fexofenadine intestinal transport and permeability were evaluated by in vitro non-everted sac and in situ single pass intestinal perfusion (SPIP) studies. These results were confirmed by an in vivo pharmacokinetic study of oral administered fexofenadine (10 mg/kg) in rats. Results: The intestinal transport and apparent permeability (P-app) of fexofenadine were significantly increased in duodenum, jejunum and ileum of diosmin pretreated group as compared with the control. Similarly effective permeability (P-eff) of fexofenadine was increased significantly in ileum of diosmin pretreated group as compared with control. In comparison with control, pretreatment with diosmin significantly increased peak plasma concentration (C-max) and area under the concentration-time curve (AUC), while there was no significant change was observed in half life (T-1/2), time to reach peak plasma concentration (T-max) and elimination rate constant (K-el) of fexofenadine. Conclusions: Diosmin significantly enhanced the oral bioavailability of fexofenadine by the inhibition of P-gp mediated drug efflux during the intestinal absorption. Co-administration of diosmin with fexofenadine can reduce the dosage and results in reduced side effects of fexofenadine. The clinical relevance of this interaction should be further evaluated in human subjects. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.