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KMID : 0043320200430121356
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Archives of Pharmacal Research
2020 Volume.43 No. 12 p.1356 ~ p.1363
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Effects of paroxetine on the pharmacokinetics of atomoxetine and its metabolites in different CYP2D6 genotypes
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Jung Eui-Hyun
Lee Yun-Jeong
Kim Dong-Hyun
Kang Pu-Reum
Lim Chang-Woo
Cho Chang-Keun
Jang Choon-Gon
Lee Seok-Yong
Bae Jung-Woo
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Abstract
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The aim of this study was to investigate the ?effects of paroxetine, a potent inhibitor of CYP2D6, on the pharmacokinetics of atomoxetine and its two metabolites, 4-hydroxyatomoxetine and N-desmethylatomoxetine, in different CYP2D6 genotypes. Twenty-six healthy subjects were recruited and divided into CYP2D6*wt/*wt (*wt=*1 or *2, n?=?10), CYP2D6*wt/*10 (n?=?9), and CYP2D6*10/*10 groups (n?=?7). In atomoxetine phase, all subjects received a single oral dose of atomoxetine (20 mg). In paroxetine phase, after administration of a single oral dose of paroxetine (20 mg) for six consecutive days, all subjects received a single oral dose of atomoxetine with paroxetine. Plasma concentrations of atomoxetine and its metabolites were determined up to 24 h after dosing. During atomoxetine phase, there were significant differences in Cmax and AUC0?24 of atomoxetine and N-desmethylatomoxetine among three genotype groups, whereas significant differences were not found in relation to CYP2D6*10 allele after administration of paroxetine. AUC ratios of 4-hydroxyatomoxetine and N-desmethylatomoxetine to atomoxetine were significantly different among three genotype groups during atomoxetine phase (all, P?
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KEYWORD
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Atomoxetine, Paroxetine, CYP2D6, Polymorphism, Pharmacokinetics
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