Pharmacokinetics of Hesperidin and its Hepatic, Gastric and Intestinal First-pass Effects in Rats

The aims of this study are to investigate the pharmacokinetics and its hepatic, gastric and intestinal first-pass effects of hesperidin (HP) in rats. A rapid and sensitive ultra-high performance liquid chromatographic method with vitexin-2 "-O-rhamnoside as the internal standard (IS) was firstly developed and validated to investigate the pharmacokinetics of HP. Secondly, the hepatic, gastric and intestinal first-pass effect models were established to investigate the reasons of the low bioavailability of HP and the results indicated that the intestinal first-pass effect was remarkable to be 61.31%. Finally, verapamil and borneol being as the inhibitors of CYP3A and P-gp, bile salt being as the absorption enhancer, were respectively administrated with HP together in order to improve the bioavailability of HP, and the results indicated that the bile salt groups remarkably improved the bioavailability of HP via inhibiting the intestinal first-pass effect.