Background: Hesperetin has antihyperuricemia activity, and the pharmacokinetic profiles
of hesperetin may be altered by hyperuricemia. This study aimed to develop a highly sensitive
and specific method for the determination of hesperetin in normal and hyperuricemia rats, and to
compare pharmacokinetic profiles of hesperetin after oral administration between normal and hyperuricemia
Methods: Sprague-Dawley (SD) rats were randomly divided into one normal group (group A) and
four hyperuricemia groups (group B, C, D, and E). Groups A, B, C, and D received a single dose
(9–81 mg/kg) of hesperetin on Day 28, respectively, while group E received multiple doses (27
mg/kg) of hesperetin once daily for 28 days. Blood samples were collected at 10 different time
points post-dose, and hesperetin was determined by Ultra-high Performance Liquid Chromatography-
tandem Mass Spectrometric (UPLC-MS/MS).
Results: Compared with normal condition of group A, hyperuricemia of group C induced 48.19%
and 19.57% decreases in Cmax and CL/F, and resulted in 58.25% and 19.48% increases in Tmax
and AUC0-t for hesperetin, respectively. After 28 days of hesperitin treatment, Cmax of group E
was significantly elevated than that of group C (p < 0.05). Hesperetin exhibited nonlinear pharmacokinetic
properties in the range of 9-81 mg/kg in hyperuricemia rats.
Conclusion: The pharmacokinetic parameters of hesperetin in hyperuricemia rats were reported for
the first time. Intestinal injury may be ameliorated by hesperetin in hyperuricemia rats after 28
days’ treatment. These findings could provide more beneficial information to the mechanism and
clinical applications of hesperetin.