The effect of resveratrol on pharmacokinetics of aripiprazole in vivo and in vitro |
| |
| Authors: | Yun-Yun Zhan Bing-Qing Liang Xiang-Yu Li Er-Min Gu Da-Peng Dai |
| |
| Institution: | 1. School of Pharmacy, Wenzhou Medical University, Wenzhou, China and;2. The Key Laboratory of Geriatrics, Beijing Hospital &3. Beijing Institute of Geriatrics, Ministry of Health, Beijing, China |
| |
| 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 Cmax of APZ. The resveratrol also obviously decreased the CL, but without any significant difference on t1/2 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. |
| |
| Keywords: | Aripiprazole CYP2D6*1 CYP3A4*1 drug interaction liver microsomes pharmacokinetics resveratrol |
|
|
