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Effects of paroxetine on the pharmacokinetics of atomoxetine and its metabolites in different CYP2D6 genotypes

Effects of paroxetine on the pharmacokinetics of atomoxetine and its metabolites in different CYP2D6 genotypes

Authors :
Eui Hyun Jung
Pureum Kang
Chang Woo Lim
Chang‑Keun Cho
Donghyun Kim
Seok-Yong Lee
Jung‑Woo Bae
Yun Jeong Lee
Choon-Gon Jang
Source :
Archives of Pharmacal Research. 43:1356-1363
Publication Year :
2020
Publisher :
Springer Science and Business Media LLC, 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 (all, P

Details

ISSN :
19763786 and 02536269
Volume :
43
Database :
OpenAIRE
Journal :
Archives of Pharmacal Research
Accession number :
edsair.doi.dedup.....38a9129c5dff6a1085ef6f38fafcd12d
Full Text :
https://doi.org/10.1007/s12272-020-01300-8