| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | International Clinical Psychopharmacology | ||||
| Publisher: | Lippincott | ||||
| Place of Publication: | PHILADELPHIA | ||||
| Volume: | 34 | ||||
| Number of Issue or Book Chapter: | 5 | ||||
| Page Range: | pp. 241-246 | ||||
| Date: | 2019 | ||||
| Institutions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie Chemistry and Pharmacy > Institute of Pharmacy | ||||
| Identification Number: |
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| Keywords: | MAJOR DEPRESSIVE DISORDER; CONSENSUS GUIDELINES; DRUG-INTERACTIONS; PLASMA-LEVELS; CYP2D6; ANTIDEPRESSANTS; POLYPHARMACY; RISPERIDONE; NEUROPSYCHOPHARMACOLOGY; PHARMACOKINETICS; antidepressant polypharmacy; cytochrome P450; interaction; pharmacokinetics; therapeutic drug monitoring; trimipramine; venlafaxine | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 48269 |
Web of ScienceAbstract
Objective The aim of this study was to ensure patients' safety and to enhance treatment efficacy, knowledge about pharmacokinetic interactions even in complex clinical situations of polypharmacy is invaluable. This study is to uncover the potential of pharmacokinetic interactions between venlafaxine and trimipramine in a naturalistic sample. Methods Out of a therapeutic drug monitoring database ...
Abstract
Objective The aim of this study was to ensure patients' safety and to enhance treatment efficacy, knowledge about pharmacokinetic interactions even in complex clinical situations of polypharmacy is invaluable. This study is to uncover the potential of pharmacokinetic interactions between venlafaxine and trimipramine in a naturalistic sample. Methods Out of a therapeutic drug monitoring database with plasma concentrations of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV), we considered two groups of patients receiving venlafaxine without known cytochrome P450 confounding medications, taking solely venlafaxine: V-0 (n = 905), and a group of patients co-medicated with trimipramine, V-TRIM (n = 33). For VEN, ODV and active moiety (sum of VEN + ODV) plasma concentrations and dose-adjusted concentrations as well as ODV/VEN ratios were compared between groups using the Mann-Whitney U test with a significance level of 0.05. Results Patients co-medicated with trimipramine had higher plasma concentrations of VEN (183.0 vs. 72.0, +154%, P = 0.002) and AM (324.0 vs. 267.5, +21%, P = 0.005) and higher dose adjusted plasma concentrations than patients in the control group (P = 0.001 and P = 0.003). No differences were found for ODV and C/D ODV (P < 0.05 for both comparisons). The metabolite to parent ratio, ODV/VEN, was significantly lower in the V-TRIM group (1.15 vs. 2.37, P = 0.012). Conclusion Findings suggest inhibitory effects of trimipramine on venlafaxine pharmacokinetics most likely via an inhibition of CYP 2D6 or by saturated enzyme capacity. The lack of in vitro data hampers the understanding of the exact mechanisms. Clinicians should be aware of drug-drug interactions when combining these agents. Therapeutic drug monitoring helps to ensure treatment efficacy and patients' safety.
Metadata last modified: 03 Sep 2021 09:47
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