Kowalewski, Christoph and Haen, Ekkehard and Hiemke, Christoph and Ridders, Florian and Endres, Katharina and Gruender, Gerhard and Paulzen, Michael and Schoretsanitis, Georgios (2019) Cytochrome P450-mediated inhibition of venlafaxine metabolism by trimipramine. INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY, 34 (5). pp. 241-246. ISSN 0268-1315, 1473-5857
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled 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 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Mar 2020 08:40 |
| Last Modified: | 30 Mar 2020 08:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26287 |
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