EFFECT OF NANONIZED CHRYSIN ON FEXOFENADINE PHARMACOKINETICS MEDIATED BY P-GLYCOPROTEIN IN RATS

Abstract

Chrysin(CHR) is an abundant flavonoid in nature and has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro, which may have the potential to alter bioavailability of P-gp substrates. The main objective of this study was to investigate the effect of nanonized chrysin (NCH) on the intestinal absorption and pharmacokinetics of P-gp probe substrate; fexofenadine in rats. NCH was prepared by antisolvent precipitation method and characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and in vitro dissolution testing. The influence of CHR and NCH on fexofenadine intestinal transport and permeability were evaluated by in vitro non-everted sac and in situ single pass intestinal perfusion (SPIP) studies. These findings were further confirmed by an in vivo pharmacokinetic study in which fexofenadine was administered (10 mg/kg, p.o) to CHR and NCH (50 mg/kg, p.o.) pretreated (10 days) rats and its plasma concentrations were determined by HPLC analysis. The intestinal transport and apparent permeability (Papp) of fexofenadine were significantly increased in duodenum, jejunum and ileum of CHR and NCH pretreated group as compared with the control. Similarly effective permeability (Peff) of fexofenadine was increased significantly in ileum of CHR and NCH pretreated group as compared with control. Cmax, AUC0-t and AUC0- ∞ of fexofenadine were found to be increased in CHR and NCH pretreated groups. Further, the CL/F and Vd/F of fexofenadine were significantly decreased. NCH enhances the oral bioavailability of fexofenadine by inhibition of P-gp mediated drug efflux during the intestinal absorption.