Tian Lan1, Xiao-Xia Hu1, Bing-Qing Liang1, Wen-He Pan1, Quan Zhou1, Ling-Jing Yuan1, Guo-Xin Hu2. 1. Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China. 2. Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China. hgx@wmu.edu.cn.
Abstract
BACKGROUND AND OBJECTIVES: 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 C max and AUC of atomoxetine, but decreased the C max and AUC of 4-hydroxyatomoxetine. Moreover, myricetin showed inhibitory effect on human and rat microsomes, the IC50 of 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.
BACKGROUND AND OBJECTIVES: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 C max and AUC of atomoxetine, but decreased the C max and AUC of 4-hydroxyatomoxetine. Moreover, myricetin showed inhibitory effect on human and rat microsomes, the IC50 of 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: John-Michael Sauer; G Douglas Ponsler; Edward L Mattiuz; Amanda J Long; Jennifer W Witcher; Holly R Thomasson; Karl A Desante Journal: Drug Metab Dispos Date: 2003-01 Impact factor: 3.922
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