title: 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 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.
authors.affiliation: a School of Pharmacy, Wenzhou Medical University , Wenzhou , China and.
authors.forename: Yun-Yun
authors.initials: YY
authors.lastname: Zhan
authors.affiliation: a School of Pharmacy, Wenzhou Medical University , Wenzhou , China and.
authors.forename: Bing-Qing
authors.initials: BQ
authors.lastname: Liang
authors.affiliation: a School of Pharmacy, Wenzhou Medical University , Wenzhou , China and.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Li
authors.affiliation: a School of Pharmacy, Wenzhou Medical University , Wenzhou , China and.
authors.forename: Er-Min
authors.initials: EM
authors.lastname: Gu
authors.affiliation: b The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health , Beijing , China.
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Dai
authors.affiliation: b The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health , Beijing , China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Cai
authors.affiliation: a School of Pharmacy, Wenzhou Medical University , Wenzhou , China and.
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Hu
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics; D019540:Area Under Curve; D000068180:Aripiprazole / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry
chemical_list: D014150:Antipsychotic Agents; D004791:Enzyme Inhibitors; D013267:Stilbenes; D000068180:Aripiprazole; C465260:Cyp3a2 protein, rat; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000077185:Resveratrol
keywords: Aripiprazole; CYP2D6*1; CYP3A4*1; drug interaction; liver microsomes; pharmacokinetics; resveratrol