Effects of paroxetine on the pharmacokinetics of atomoxetine and its metabolites in different CYP2D6 genotypes
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Online ISSN 1976-3786 Print ISSN 0253-6269
RESEARCH ARTICLE
Effects of paroxetine on the pharmacokinetics of atomoxetine and its metabolites in different CYP2D6 genotypes Eui Hyun Jung1 · Yun Jeong Lee2 · Dong‑Hyun Kim1 · Pureum Kang1 · Chang Woo Lim1 · Chang‑Keun Cho1 · Choon‑Gon Jang1 · Seok‑Yong Lee1 · Jung‑Woo Bae3
Received: 18 November 2020 / Accepted: 23 November 2020 © The Pharmaceutical Society of Korea 2020
Abstract 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
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