Dose-Dependent Inhibition of CYP2D6 by Bupropion in Patients With Depression
| Autor: | Espen Molden, Kristine Hole, Tore Haslemo, Marianne Arnestad |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty CYP2D6 Genotype Venlafaxine digestive system Gastroenterology Young Adult 03 medical and health sciences 0302 clinical medicine Cytochrome P-450 CYP2D6 Inhibitors Desvenlafaxine Succinate Internal medicine medicine Humans Pharmacology (medical) Clinical significance Dosing skin and connective tissue diseases Bupropion Depression (differential diagnoses) Aged Retrospective Studies Aged 80 and over Dose-Response Relationship Drug medicine.diagnostic_test Depression business.industry Venlafaxine Hydrochloride Middle Aged 030227 psychiatry Psychiatry and Mental health Cytochrome P-450 CYP2D6 Therapeutic drug monitoring Antidepressive Agents Second-Generation Biomarker (medicine) Female Drug Monitoring business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Clinical Psychopharmacology. 41:281-285 |
| ISSN: | 1533-712X 0271-0749 |
| Popis: | PURPOSE The aim of this study was to investigate the potential dose-dependent CYP2D6 inhibition by bupropion (BUP) in patients with depression. METHODS 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. FINDINGS 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. CONCLUSIONS 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. |
| Databáze: | OpenAIRE |
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