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

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.

KEYWORDS:

• CYP3A4
• ibrutinib
• liver microsomes
• metabolism
• resveratrol

Disclosure statement

No potential conflict of interest was reported by the authors.

All authors thank the partner and funding from Wenzhou Medical University and the Beijing Hospital Nova Project (BJ-2016-034 to J.C).