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Comparative Pharmacokinetic Study of Hesperetin after Oral Administration in Normal and Hyperuricemia Rats by UPLC-MS/MS

[ Vol. 15 , Issue. ]

Author(s):

Kexin Li, Li Wei, Zhigang Han, Huarong Xiong, Fengmei Zhang, Xuwei Liu, Dezhang Zhao, Yongquan Pan and Wenli Han* Pages 1-7 (7)

Abstract:


Backgrounds: 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 rats.

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.

Conclusions: 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.

Keywords:

Hesperetin, Hyperuricemia rat, Intestinal impairments, Pharmacokinetic, UPLC-MS/MS, flavanone

Affiliation:

Laboratory Animal Center, Chongqing Medical University, Chongqing, Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, Chongqing, Laboratory Animal Center, Chongqing Medical University, Chongqing, Department of Pharmacy, Chengdu First People's Hospital, Chengdu, Laboratory Animal Center, Chongqing Medical University, Chongqing, Department of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, College of Pharmacy, Chongqing Medical University, Chongqing, Laboratory Animal Center, Chongqing Medical University, Chongqing, Laboratory Animal Center, Chongqing Medical University, Chongqing



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