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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
- 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
- Subjects :
- Adult
Male
0301 basic medicine
CYP2D6
Genotype
Pharmacogenomic Variants
Cmax
Administration, Oral
Pharmacology
Atomoxetine Hydrochloride
Models, Biological
digestive system
Single oral dose
Young Adult
03 medical and health sciences
0302 clinical medicine
Phenols
Pharmacokinetics
Cytochrome P-450 CYP2D6 Inhibitors
Drug Discovery
medicine
Humans
Drug Interactions
Dosing
skin and connective tissue diseases
Biotransformation
Propylamines
business.industry
Phenyl Ethers
Organic Chemistry
Atomoxetine
Paroxetine
030104 developmental biology
Cytochrome P-450 CYP2D6
Pharmacogenetics
030220 oncology & carcinogenesis
Molecular Medicine
Female
business
medicine.drug
Subjects
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