1. The Impact of Baohuoside I on the Metabolism of Tofacitinib in Rats
- Author
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Shi,Yaru, Lu,Zebei, Song,Wei, Wang,Yu, Zhou,Quan, Geng,Peiwu, Zhou,Yunfang, Wang,Shuanghu, Han,Aixia, Shi,Yaru, Lu,Zebei, Song,Wei, Wang,Yu, Zhou,Quan, Geng,Peiwu, Zhou,Yunfang, Wang,Shuanghu, and Han,Aixia
- Abstract
Yaru Shi,* Zebei Lu,* Wei Song, Yu Wang, Quan Zhou, Peiwu Geng, Yunfang Zhou, Shuanghu Wang, Aixia Han Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui Peopleâs Hospital, Lishui, Zhejiang, 323000, Peopleâs Republic of China*These authors contributed equally to this workCorrespondence: Aixia Han; Shuanghu Wang, Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui Peopleâs Hospital, Lishui, Zhejiang, 323000, Peopleâs Republic of China, Tel +86 5782780081, Email hanaixia1316@163.com; wangshuanghu@lsu.edu.cnPurpose: To study the potential drugâdrug interactions between tofacitinib and baohuoside I and to provide the scientific basis for rational use of them in clinical practice.Methods: A total of eighteen Sprague-Dawley rats were randomly divided into three groups: control group, single-dose group (receiving a single dose of 20 mg/kg of baohuoside I), and multi-dose group (receiving multiple doses of baohuoside I for 7 days). On the seventh day, each rat was orally administered with 10 mg/kg of tofacitinib 30 minutes after giving baohuoside I or vehicle. Blood samples were collected and determined using UPLC-MS/MS. In vitro effects of baohuoside I on tofacitinib was investigated in rat liver microsomes (RLMs), as well as the underlying mechanism of inhibition. The semi-inhibitory concentration value (IC50) of baohuoside I was subsequently determined and its inhibitory mechanism against tofacitinib was analyzed. Furthermore, the interactions between baohuoside I, tofacitinib and CYP3A4 were explored using Pymol molecular docking simulation.Results: The administration of baohuoside I orally has been observed to enhance the area under the concentration-time curve (AUC) of tofacitinib and decrease the cleara
- Published
- 2024