Zusammenfassung
Hintergrund
Unerwünschte Arzneimittelwirkungen (UAWs) haben eine hohe sozioökonomische Relevanz und erfordern eine effektive Prävention. Neben prozessbedingten vermeidbaren Fehlern sind für den personalisierten Ansatz zur Vermeidung von UAWs auch genetische Polymorphismen zu berücksichtigen.
Ziel
An 5 Kasuistiken wird exemplarisch für einige Therapiemodalitäten die klinische Bedeutung prospektiver Testungen zur Abschätzung des individuellen Risikos suszeptibler Personen dargestellt.
Material und Methoden
Die Rolle des HLA-Systems, der Cytochrom-P450-Familie, weiterer Metabolisierungsenzyme und von Transportproteinen wird zur Verdeutlichung der Bandbreite genetischer Suszeptibilität beschrieben. Warum, wann und für wen prätherapeutische Tests auf genetische Polymorphismen zur Risikominimierung von UAWs derzeit empfohlen werden, wird aufgezeigt.
Ergebnisse
1) Vor einer Therapie bei Südostasiaten mit Carbamazepin und 2) vor der Behandlung von Personen – unabhängig von ihrer ethnischen Herkunft – mit Abacavir ist die Bestimmung der genetischen Suszeptibilität schon heute in der ärztlichen Praxis etabliert und sollte für die Therapieentscheidung herangezogen werden.
Schlussfolgerung
Über die breite Anwendung personalisierter Medizin als wirksames Instrument zur Vermeidung von UAWs entscheidet die Relation zwischen dem evidenzbasierten Nutzen für den Patienten einerseits und den Kosten eines Testes andererseits.
Abstract
Background
Because adverse drug events (ADEs) have a high socio-economic impact there is an urgent need for effective prevention. In addition to process-related avoidable errors personalised approaches for the prevention of ADEs should also focus on genetic polymorphisms as potential causative agents.
Aim
Using five case reports as examples therapeutic modalities are described to illustrate the clinical impact of prospective testing aimed at estimating the individual risk of susceptible subjects.
Material and methods
The role of the HLA system, the cytochrome P450 family, other metabolic enzymes and transport proteins are described to illustrate the broad range of genetic susceptibility. It is shown, why, when and for whom pretherapeutic tests on genetic polymorphisms are recommended to reduce the risk of ADEs.
Results
The determination of genetic susceptibility is already implemented in clinical practice prior to (1) carbamazepine therapy in south-east Asians and (2) treatment with abacavir independent of ethnicity. Before prescribing carbamazepine or abacavir, it is recommended that therapeutic decisions be based on these test results.
Conclusion
The broad application of personalised medicine used as an effective tool for minimizing ADE risks is limited by the evidence-based benefit for the patient on the one hand and the costs of the test on the other hand.
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Danksagung
Die Autoren danken Frau Karin Holz für die wertvolle Unterstützung bei der Erstellung des Manuskriptes.
Einhaltung ethischer Richtlinien
Interessenkonflikt. R. Lux, S. Wärntges, S. Bergner und B. Kütting geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
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Lux, R., Wärntges, S., Bergner, S. et al. Erhöhung der Arzneimitteltherapiesicherheit durch Identifizierung genetisch prädisponierter Personen. Bundesgesundheitsbl. 56, 1545–1556 (2013). https://doi.org/10.1007/s00103-013-1827-x
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DOI: https://doi.org/10.1007/s00103-013-1827-x
Schlüsselwörter
- Personalisierte Medizin
- Vermeidung von unerwünschten Arzneimittelwirkungen
- Arzneimitteltherapiesicherheit
- Genetische Polymorphismen
- Suszeptibilität