Hefner, Gudrun and Unterecker, Stefan and Shams, Mohamed E. E. and Wolf, Margarete and Falter, Tanja and Haen, Ekkehard and Hiemke, Christoph (2015) Melperone but not bisoprolol or metoprolol is a clinically relevant inhibitor of CYP2D6: evidence from a therapeutic drug monitoring survey. JOURNAL OF NEURAL TRANSMISSION, 122 (11). pp. 1609-1617. ISSN 0300-9564, 1435-1463
Full text not available from this repository. (Request a copy)Abstract
Cytochrome P450 enzymes (CYP) can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures. The objective of the study was to analyze the in vivo inhibitory potential of the beta-blockers bisoprolol and metoprolol as well as the low-potency antipsychotic melperone on CYP2D6. By utilizing a large therapeutic drug monitoring database of 2874 samples, data from patients who had been treated with venlafaxine (VEN) either without (control group) or with a concomitant medication with bisoprolol, metoprolol or melperone were evaluated retrospectively to study the CYP2D6-catalyzed O-demethylation to O-desmethylvenlafaxine (ODVEN). Dose-adjusted serum levels (C/D) of VEN and ODVEN as well as the metabolic ratios (ODVEN/VEN) were computed for the four groups and compared using Kruskal-Wallis test. In total, 381 patients could be included for analysis. No significant difference was found in the median C/D (VEN), C/D (ODVEN) or C/D of the active moiety (VEN + ODVEN) in either the metoprolol (N = 103) or bisoprolol group (N = 101), compared to the control group (N = 108). In contrast, a significantly higher median C/D (VEN) (0.79 ng/ml/mg, range 0.13-5.73 ng/ml/mg) (P < 0.01) was found in the melperone group (N = 69), compared to the control group (0.46 ng/ml/mg, range 0.02-7.39 ng/ml/mg). A significant decrease (P < 0.01) was solely found in the median metabolic ratios of ODVEN/VEN between the melperone group (0.90, range 0.14-15.15), compared to the control group (2.39, range 0.06-15.31). The results of this study provided evidence that melperone but not bisoprolol or metoprolol has a clinically relevant inhibitory potential on CYP2D6.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BETA-ADRENOCEPTOR ANTAGONISTS; MAJOR DEPRESSIVE DISORDER; HUMAN-LIVER; SPARTEINE OXIDATION; IN-VITRO; VENLAFAXINE; METABOLISM; 2D6; PHARMACOKINETICS; ANTIDEPRESSANTS; Therapeutic drug monitoring; Venlafaxine; CYP2D6; Metoprolol; Melperone; Bisoprolol |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 May 2019 07:08 |
| Last Modified: | 08 May 2019 07:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4565 |
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