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  2. Melperone but not bisoprolol or metoprolol is a clinically relevant inhibitor of CYP2D6: evidence from a therapeutic drug monitoring survey

Melperone but not bisoprolol or metoprolol is a clinically relevant inhibitor of CYP2D6: evidence from a therapeutic drug monitoring survey

  • J Neural Transm (Vienna). 2015 Nov;122(11):1609-17. doi: 10.1007/s00702-015-1403-7.
Gudrun Hefner 1 2 Stefan Unterecker 3 Mohamed E E Shams 4 5 Margarete Wolf 6 Tanja Falter 7 Ekkehard Haen 6 Christoph Hiemke 8
Affiliations

Affiliations

  • 1 Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Mainz, Germany. gudrun.hefner@unimedizin-mainz.de.
  • 2 Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany. gudrun.hefner@unimedizin-mainz.de.
  • 3 Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
  • 4 Department of Pharmaceutics, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt.
  • 5 Department of Pharmacy Practice, Ministry of Health, College of Health Sciences, Muscat, Oman.
  • 6 Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
  • 7 Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.
  • 8 Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Mainz, Germany.
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.

Keywords

Bisoprolol; CYP2D6; Melperone; Metoprolol; Therapeutic drug monitoring; Venlafaxine.

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