Inhibitory effect of resveratrol on the pharmacokinetic of ibrutinib by UPLC–MS/MS. (2nd January 2019)

• Record Type: Journal Article
• Authors: Wen, Jian; Bao, Su-Su; Zhang, Bo-Wen; Liu, Teng-Hui; Ou-Yang, Qiu-Geng; Cai, Jian-Ping; Zhou, Hong-Yu
• Is Part Of: Drug development and industrial pharmacy. Volume 45:Number 1(2019)
• Page Start: 27
• Page End: 31
• Publication Date: 2019-01-02
• Subjects: CYP3A4 -- ibrutinib -- liver microsomes -- metabolism -- resveratrol; Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.1080/03639045.2018.1514044
• Languages: English
• ISSNs: 0363-9045

Abstract

Abstract: Objective: To investigate the impact of resveratrol on the metabolism of ibrutinib in vitro and in vivo . Methods: In vitro, rat liver microsomes (RLM) and human liver microsomes (HLM) were used to study. In vivo, 18 male SD rats were randomly divided into three groups ( n = 6): ibrutinib and the multiple dose of 100 mg/kg resveratrol for consecutive 7 days (Group A), ibrutinib and the single dose of 100 mg/kg resveratrol (Group B), ibrutinib (Group C). Processed samples were analyzed by UPLC–MS/MS. Results: Resveratrol showed inhibition on RLM and HLM in vitro . The IC50 of resveratrol was 8.745 µM in RLM and 7.789 µM in HLM. Furthermore, Groups A and B both increased the AUC and reduced the CLz/ F . The C max of Group A and the MRT(0– t ) of Group B were significantly improved. Conclusions: Resveratrol inhibits the pharmacokinetic of ibrutinib in vitro and in vivo . It is necessary to pay more attention to adjust the dose of the drug when resveratrol is used in combination with ibrutinib.