Effect of CYP2D6 genotype on duloxetine serum concentration.
CYP2D6
age
duloxetine
genotype
sex
Journal
Basic & clinical pharmacology & toxicology
ISSN: 1742-7843
Titre abrégé: Basic Clin Pharmacol Toxicol
Pays: England
ID NLM: 101208422
Informations de publication
Date de publication:
20 Oct 2023
20 Oct 2023
Historique:
revised:
11
10
2023
received:
25
08
2023
accepted:
16
10
2023
pubmed:
21
10
2023
medline:
21
10
2023
entrez:
21
10
2023
Statut:
aheadofprint
Résumé
Duloxetine is metabolized by cytochrome P450 (CYP)1A2 and CYP2D6. The aim of this study was to investigate the effect of the CYP2D6 genotype on duloxetine serum concentration adjusting for age and sex. Patients were included retrospectively from a therapeutic drug monitoring service. Multiple linear regression analysis was used to investigate the effect of CYP2D6 genotype, age and sex on the duloxetine concentration-to-dose (C/D) ratio. In total, 269 patients were included and assigned to the following genotype-predicted phenotype subgroups: CYP2D6 poor metabolizers (PMs, n = 23), intermediate metabolizers (IMs, n = 121), normal metabolizers (NMs, n = 120) and ultrarapid metabolizers (UMs, n = 5). Multiple linear regression analysis revealed a 95% higher duloxetine C/D ratio in PMs compared with NMs (p = 0.009). Patients ≥65 years had a 56% higher C/D ratio than younger patients (p = 0.01), while women had a 46% higher C/D ratio than men (p = 0.04). In conclusion, the CYP2D6 PM phenotype is associated with a twofold higher concentration at recommended dosing compared with the NM phenotype. CYP2D6 PM females above 65 years are at particular risk of high duloxetine levels as they may obtain a threefold higher C/D ratio compared with younger, male NMs.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : ERA PerMed
ID : ERAPERMED2021-357
Informations de copyright
© 2023 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
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