title: The Effect of Myricetin on Pharmacokinetics of Atomoxetine and its Metabolite 4-Hydroxyatomoxetine In Vivo and In Vitro.
abstract: OBJECTIVE
  Atomoxetine is the first non-stimulant drug to be approved for the treatment of ADHD, while the effect of myricetin on the pharmacokinetic of atomoxetine in rats or human is still unknown. The present work was to study the impact of myricetin on the metabolism of atomoxetine both in vivo and in vitro.
  
  
  METHODS
  Twenty healthy male Sprague-Dawley rats were randomly divided into four groups: A (control group), B (100 mg/kg myricetin), C (50 mg/kg myricetin), and D (25 mg/kg myricetin). A single dose of atomoxetine (10 mg/kg) was administrated half an hour later. In addition, human and rat liver microsomes were performed to determine the effect of myricetin on the metabolism of atomoxetine in vitro.
  
  
  RESULTS
  Group B, C, D all increased the Cmaxand AUC of atomoxetine, but decreased the Cmaxand AUC of 4-hydroxyatomoxetine. Moreover, myricetin showed inhibitory effect on human and rat microsomes, the IC50of myricetin was 8.651 and 35.45 µmol/L, respectively.
  
  
  CONCLUSIONS
  Our study showed that myricetin could significantly inhibit the formation of atomoxetine metabolite both in vivo and in vitro. It is recommended that the effect of myricetin on the metabolism of atomoxetine should be noted and atomoxetine plasma concentration should be monitored.
authors.affiliation: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Lan
authors.affiliation: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
authors.forename: Bing-Qing
authors.initials: BQ
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
authors.forename: Wen-He
authors.initials: WH
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
authors.forename: Ling-Jing
authors.initials: LJ
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China. hgx@wmu.edu.cn.
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Hu
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D000069445:Atomoxetine Hydrochloride / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010636:Phenols / Q000493:pharmacokinetics*; D011437:Propylamines / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018759:Adrenergic Uptake Inhibitors; D005419:Flavonoids; D010636:Phenols; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; C454679:4-hydroxyatomoxetine; C040015:myricetin