Discovering interactions in polypharmacy: Impact of metamizole on the metabolism of quetiapine.

Autor: Watermeyer F; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital RWTH Aachen, Aachen, Germany.; JARA-Translational Brain Medicine, RWTH Aachen University, Aachen, Germany., Gaebler AJ; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital RWTH Aachen, Aachen, Germany.; JARA-Translational Brain Medicine, RWTH Aachen University, Aachen, Germany.; Institute of Physiology, University Hospital RWTH Aachen, Aachen, Germany., Neuner I; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital RWTH Aachen, Aachen, Germany.; JARA-Translational Brain Medicine, RWTH Aachen University, Aachen, Germany., Haen E; Department of Psychiatry and Psychotherapy, Clinical Pharmacology, University of Regensburg, Regensburg, Germany.; Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.; Clinical Pharmacology Institute AGATE gGmbH, Pentling, Germany., Hiemke C; Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Mainz, Germany., Schoretsanitis G; Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich, Zürich, Switzerland.; University of Zurich, Zurich, Switzerland.; Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, USA., Paulzen M; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital RWTH Aachen, Aachen, Germany.; JARA-Translational Brain Medicine, RWTH Aachen University, Aachen, Germany.; Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.; Alexianer Hospital Aachen, Aachen, Germany.
Jazyk: angličtina
Zdroj: British journal of clinical pharmacology [Br J Clin Pharmacol] 2024 Nov; Vol. 90 (11), pp. 2793-2801. Date of Electronic Publication: 2024 Jul 06.
DOI: 10.1111/bcp.16168
Abstrakt: Aims: Metamizole is quite an old drug with analgesic, antipyretic and spasmolytic properties. Recent findings have shown that it may induce several cytochrome P450 (CYP) enzymes, especially CYP3A4 and CYP2B6. The clinical relevance of these properties is uncertain. We aimed to unravel potential pharmacokinetic interactions between metamizole and the CYP3A4 substrate quetiapine.
Methods: Plasma concentrations of quetiapine from a large therapeutic drug monitoring database were analysed. Two groups of 33 patients, either receiving quetiapine as a monotherapy (without CYP modulating comedications) or with concomitantly applied metamizole, were compared addressing a potential impact of metamizole on the metabolism of quetiapine being reflected in differences of plasma concentrations of quetiapine and dose-adjusted plasma concentrations.
Results: Patients comedicated with metamizole showed >50% lower plasma concentrations of quetiapine (median 45.2 ng/mL, Q 1  = 15.5; Q 3  = 90.5 vs. 92.0 ng/mL, Q 1  = 52.3; Q 3  = 203.8, P = .003). The dose-adjusted plasma concentrations were 69% lower in the comedication group (P = .001). Subgroup analyses did not suggest a dose dependency of the metamizole effect or an influence of quetiapine formulation (immediate vs. extended release). Finally, the comedication group exhibited a significantly higher proportion of patients whose quetiapine concentrations were below the therapeutic reference range (78.8% in the metamizole group vs. 54.4% in the control group, P = .037) indicating therapeutically insufficient drug concentrations.
Conclusion: The combination of metamizole and quetiapine leads to significantly lower drug concentrations of quetiapine, probably via an induction of CYP3A4. Clinicians must consider the risk of adverse drug reactions, especially treatment failure under quetiapine when adding metamizole.
(© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)
Databáze: MEDLINE
Externí odkaz: