Dose-Dependent Inhibition of CYP2D6 by Bupropion in Patients With Depression.
Adult
Aged
Aged, 80 and over
Antidepressive Agents, Second-Generation
/ administration & dosage
Bupropion
/ administration & dosage
Cytochrome P-450 CYP2D6
/ drug effects
Cytochrome P-450 CYP2D6 Inhibitors
/ administration & dosage
Depression
/ drug therapy
Desvenlafaxine Succinate
/ pharmacokinetics
Dose-Response Relationship, Drug
Drug Monitoring
Female
Genotype
Humans
Male
Middle Aged
Retrospective Studies
Venlafaxine Hydrochloride
/ administration & dosage
Young Adult
Journal
Journal of clinical psychopharmacology
ISSN: 1533-712X
Titre abrégé: J Clin Psychopharmacol
Pays: United States
ID NLM: 8109496
Informations de publication
Date de publication:
Historique:
entrez:
27
4
2021
pubmed:
28
4
2021
medline:
10
11
2021
Statut:
ppublish
Résumé
The aim of this study was to investigate the potential dose-dependent CYP2D6 inhibition by bupropion (BUP) in patients with depression. Patients combining BUP with venlafaxine were included from a therapeutic drug monitoring (TDM) database at the Diakonhjemmet Hospital (Oslo, Norway). The O/N-desmethylvenlafaxine metabolic ratio measured in TDM samples was used as a biomarker for CYP2D6 phenotype and was compared between patients treated with BUP 150 mg/d and 300 mg/d or greater. In addition, reference groups of venlafaxine-treated patients genotyped as CYP2D6 poor metabolizers (PMs, no CYP2D6 activity) and normal metabolizers (NMs, fully functional CYP2D6 activity) were included. A total of 221 patients were included in the study. The median O/N-desmethylvenlafaxine metabolic ratio was significantly higher in patients treated with BUP 150 mg/d (n = 59) versus 300 mg/d or greater (n = 34, 1.77 vs 0.96, P < 0.001). In CYP2D6 NMs (n = 62) and PMs (n = 66), the median metabolic ratios were 40.55 and 0.48, respectively. For patients treated with BUP 150 mg/d, 11 (19%) of the 59 patients were phenoconverted to PMs, whereas this was the case for 17 (50%) of the 34 patients treated with BUP 300 mg/d or greater. Bupropion exhibits a clear dose-dependent CYP2D6 inhibitory effect during treatment of patients with depression. This finding is of clinical relevance when adjusting dosing of CYP2D6 substrates during comedication with BUP. Half of the patients treated with high-dose BUP are converted to CYP2D6 PM phenotype. Because of the variability in CYP2D6 inhibition, TDM of CYP2D6 substrates should be considered to provide individualized dose adjustments during comedication with BUP.
Identifiants
pubmed: 33905640
doi: 10.1097/JCP.0000000000001387
pii: 00004714-202105000-00010
doi:
Substances chimiques
Antidepressive Agents, Second-Generation
0
Cytochrome P-450 CYP2D6 Inhibitors
0
Bupropion
01ZG3TPX31
Venlafaxine Hydrochloride
7D7RX5A8MO
Cytochrome P-450 CYP2D6
EC 1.14.14.1
Desvenlafaxine Succinate
ZB22ENF0XR
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
281-285Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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