The effect of resveratrol on pharmacokinetics of aripiprazole in vivo and in vitro

Abstract

1. The objective of this study were to investigate the effect of orally administered resveratrol on the pharmacokinetics of aripiprazole (APZ) in rat, and the inhibitory effects of resveratrol on APZ dehydrogenation activity in liver microsomes and human cytochrome P450 3A4 and 2D6.

2. Twenty-five healthy male Sprague–Dawley rats were randomly divided into five groups: A (control group), B (multiple dose of 200 mg/kg resveratrol), C (multiple dose of 100 mg/kg resveratrol), D (a single dose of 200 mg/kg resveratrol) and E (a single dose of 100 mg/kg resveratrol). A single dose of 3 mg/kg APZ administered orally 30 min after administration of resveratrol. In addition, CYP2D6*1, CYP3A4*1, human and rat liver microsomes were performed to determine the effect of resveratrol on the metabolism of APZ in vitro.

3. The multiple dose of 200 or 100 mg/kg resveratrol significantly increased the AUC and C_max of APZ. The resveratrol also obviously decreased the CL, but without any significant difference on t_1/2 in vivo. On the other hand, resveratrol showed inhibitory effect on CYP3A4*1, CYP2D6*1, human and rat microsomes, the IC₅₀ of resveratrol was 6.771, 87.87, 45.11 and 35.59 μmol l⁻¹, respectively.

4. Those results indicated more attention should be paid when APZ was administrated combined with resveratrol.

• Aripiprazole
• CYP2D6*1
• CYP3A4*1
• drug interaction
• liver microsomes
• pharmacokinetics
• resveratrol

Acknowledgements

We are grateful to the members of the Beijing Institute of Geriatrics of the Ministry of Health for their advice and assistance.

Declaration of interest

This work was supported by a grant from the National Health and Family Planning Commission of the People’s Republic of China (No 201302008). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.