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CC BY 4.0 · Aktuelle Urol
DOI: 10.1055/a-2593-1605
Übersicht

Androgenrezeptor-gerichtete Therapien – klinisch relevante Interaktionen vermeiden

Androgen receptor-targeted therapies – avoid clinically relevant interactions
Hans-Peter Lipp
1   Lehrbeauftragter für Pharmaökonomie und -epidemiologie, Pharmazeutisches Institut, Universität Tübingen, Tübingen, Germany
,
Gunhild von Amsberg
2   Onkologisches Zentrum/ Martini-Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany (Ringgold ID: RIN37734)
,
Axel S. Merseburger
3   Urology, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
,
Steffen Rausch
4   Klinik für Urologie, Universitätsklinik Tübingen, Tübingen, Germany
,
Tilman Schöning
5   Universitätsapotheke, Universitätsklinikum Heidelberg, Heidelberg, Germany (Ringgold ID: RIN27178)
,
Jörg Klier
6   Urologie, Urologie Bayenthal in Köln, Köln, Germany
,
Peter J. Goebell
7   Urologische und kinderurologische Klinik, Universitätsklinikum Erlangen, Erlangen, Germany
› Institutsangaben
Dieses Manuskript wurde mit Unterstützung von Medical Writern erstellt. Diese Leistungen wurden von Bayer Vital GmbH finanziert.
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Zusammenfassung

Die Behandlung älterer Patienten erfordert eine besondere Aufmerksamkeit für Arzneimittelinteraktionen, da mit einer Zunahme der altersbedingten Morbidität eine Polypharmazie immer relevanter wird. Insbesondere bei Medikamenten mit einer geringen therapeutischen Breite können Arzneimittelinteraktionen klinische Konsequenzen haben, die eine Anpassung der Dosis oder das Beenden oder Wechseln der Begleitmedikation erfordern. Oft sind diese Interaktionen auf eine pharmakokinetische Veränderung des Arzneimittelabbaus über das Cytochrom-P450(CYP)-Enzymsystem zurückzuführen, vor allem über CYP3A4. Diese Enzymisoform ist an dem Metabolismus von etwa der Hälfte der therapeutisch verwendeten Arzneimittel beteiligt, sodass sich auch viele CYP3A4-Substrate unter den eingesetzten Medikamenten bei Prostatakrebspatienten befinden. Unter den starken CYP3A4-Induktoren Apalutamid und Enzalutamid sind in diesem Zusammenhang – im Gegensatz zu Darolutamid – in vielen Fällen deutlich erniedrigte Plasmakonzentrationen bei den gleichzeitig verabreichten Arzneimitteln zu erwarten. Bei Abirateron handelt es sich hingegen um einen moderaten CYP2D6-Inhibitor. Da über dieses Isoenzym deutlich weniger Wirkstoffe biotransformiert werden, ist das Interaktionsspektrum anders zu bewerten. Um im Vorfeld einer Pharmakotherapie das Ausmaß einer Wechselwirkung besser abschätzen zu können, ist es hilfreich, die Abbauwege der einzelnen Wirkstoffe besser zu verstehen, um im Zweifel rechtzeitig das Therapiemonitoring intensivieren, Dosisveränderungen und Wechsel einer Pharmakotherapie vornehmen zu können.

Abstract

Pharmacotherapy of older patients requires special attention to drug interactions, based on an increase in morbidity and elevated need for polypharmacy. Especially for drugs with a narrow therapeutic index, interactions may require dose adjustments, discontinuation or switching of co-medication. These interactions are frequently based on pharmacokinetic alterations of drug metabolism via the cytochrome P450 (CYP) enzyme system, mainly via CYP3A4. This isoform is involved in the metabolism of about half of therapeutically applied drugs, including many agents commonly used in patients with prostate cancer. As a consequence, an impressive decrease in plasma levels of coadministered drugs has to be expected during the use of the potent CYP3A4 inducers apalutamide as well as enzalutamide, in contrast to the mild CYP3A4 inducer darolutamide. Abiraterone is classified as a moderate inhibitor of the CYP2D6 isozyme, which catalyses the biotransformation of fewer drugs. As a consequence, abiraterone’s spectrum of interaction has to be interpreted differently. As pharmacotherapy approaches, it is helpful to understand the drug biotransformation pathways in more detail, in order to assess the extent of possible interactions that may necessitate the intensification of therapeutic monitoring, or dose modification or any therapeutic switch in time.

Fazit

Medikamenteninteraktionen müssen frühzeitig erkannt werden, um Schaden vom Patienten abzuwenden.

Schlüsselwörter

Prostatakarzinom - Arzneimittelinteraktionen - Polypharmazie - Pharmakokinetik - Cytochrom-P450-Enzymsystem

Keywords

prostate cancer - drug interactions - polypharmacy - pharmacokinetics - cytochrome P450 enzyme system


Publikationsverlauf

Eingereicht: 04. September 2024

Angenommen nach Revision: 08. April 2025

Artikel online veröffentlicht:
04. Juni 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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