Inhibitory effect of resveratrol on the pharmacokinetic of ibrutinib by UPLC-MS/MS

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 mult...

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Published in:Drug development and industrial pharmacy 2019-01, Vol.45 (1), p.27-31
Main Authors: Wen, Jian, Bao, Su-Su, Zhang, Bo-Wen, Liu, Teng-Hui, Ou-Yang, Qiu-Geng, Cai, Jian-Ping, Zhou, Hong-Yu
Format: Article
Language:English
Subjects:
Animals
Antioxidants - analysis
Antioxidants - pharmacokinetics
Chromatography, High Pressure Liquid - methods
CYP3A4
Dose-Response Relationship, Drug
Drug Interactions - physiology
Humans
ibrutinib
liver microsomes
Male
metabolism
Microsomes, Liver - drug effects
Microsomes, Liver - metabolism
Pyrazoles - analysis
Pyrazoles - pharmacokinetics
Pyrimidines - analysis
Pyrimidines - pharmacokinetics
Random Allocation
Rats
Rats, Sprague-Dawley
resveratrol
Resveratrol - analysis
Resveratrol - pharmacokinetics
Tandem Mass Spectrometry - methods
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Summary: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 IC 50 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.
ISSN:0363-9045
1520-5762
DOI:10.1080/03639045.2018.1514044