Melperone but not bisoprolol or metoprolol is a clinically relevant inhibitor of CYP2D6: evidence from a therapeutic drug monitoring survey.
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.
Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Mainz, Germany. gudrun.hefner@unimedizin-mainz.de.|Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany. gudrun.hefner@unimedizin-mainz.de.
Gudrun
G
Hefner
Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
Stefan
S
Unterecker
Department of Pharmaceutics, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt.|Department of Pharmacy Practice, Ministry of Health, College of Health Sciences, Muscat, Oman.
Mohamed E E
ME
Shams
Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
Margarete
M
Wolf
Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.
Tanja
T
Falter
Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
Ekkehard
E
Haen
Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Mainz, Germany.
Christoph
C
Hiemke
D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017298:Bisoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D002090:Butyrophenones / Q000494:pharmacology / Q000627:therapeutic use*; D065690:Cytochrome P-450 CYP2D6 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D062313:Databases, Pharmaceutical; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D000069470:Venlafaxine Hydrochloride / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
D058671:Adrenergic beta-1 Receptor Antagonists; D014150:Antipsychotic Agents; D002090:Butyrophenones; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; D008790:Metoprolol; C008522:metylperon; D017298:Bisoprolol
Bisoprolol; CYP2D6; Melperone; Metoprolol; Therapeutic drug monitoring; Venlafaxine