Die Bedeutung der Kombination von Pharmakodynamik und Pharmakoepidemiologie für das Verständnis und die Verbesserung der Arzneimittelsicherheit

ZUSAMMENFASSUNG

Gegenstand und Ziel Die vorliegende Arbeit untersucht den kombinierten Ansatz von Pharmakoepidemiologie und Pharmakodynamik hinsichtlich seines Potenzials, das Verständnis und die Verbesserung der Arzneimittelsicherheit zu fördern.

Material und Methoden Die vorliegende narrative Übersichtsarbeit basiert auf einer umfassenden Literaturrecherche in der bibliografischen Datenbank MEDLINE. Der Fokus liegt auf Studien, die pharmakodynamische und pharmakoepidemiologische Daten integrieren.

Ergebnisse Die Integration pharmakodynamischer Daten, wie Rezeptorbindungsaffinitäten, mit pharmakoepidemiologischen Daten aus Spontanmeldedatenbanken hat bedeutende Erkenntnisse über die Mechanismen hinter Arzneimittelnebenwirkungen geliefert. In diesem Kontext haben Studien Korrelationen zwischen Rezeptoraffinitäten und unerwünschten Arzneimittelwirkungen aufgezeigt. Exemplarisch seien die Affinität zum Serotonintransporter und Blutungen sowie die Affinität zum Histamin-H1-Rezeptor und Diabetes genannt. Diese Erkenntnisse tragen zu einer Verbesserung unseres Verständnisses der Sicherheitsprofile von Arzneimitteln bei.

Schlussfolgerungen und klinische Relevanz Der pharmakodynamisch-pharmakoepidemiologische Ansatz ermöglicht wertvolle Einblicke in die Mechanismen und Risiken von Arzneimittelnebenwirkungen, insbesondere in der Psychopharmakologie.

ABSTRACT

Objective This paper examines the combined approach of pharmacoepidemiology and pharmacodynamics in terms of its potential to advance the understanding and improvement of drug safety.

Material and methods This narrative review is based on a comprehensive literature search in the MEDLINE bibliographic database. The focus is on studies that integrate pharmacodynamic and pharmacoepidemiologic data.

Results The integration of pharmacodynamic data, such as receptor binding affinities, with pharmacoepidemiologic data from spontaneous reporting databases has provided significant insights into the mechanisms behind adverse drug reactions. In this context, studies have shown correlations between receptor affinities and adverse drug reactions. Examples include affinity for the serotonin transporter and bleeding and affinity for the histamine H1 receptor and diabetes. These findings contribute to improving our understanding of the safety profiles of drugs.

Conclusion The pharmacodynamic-pharmacoepidemiological approach provides valuable insights into the mechanisms and risks of drug side effects, especially in psychopharmacology.

Schlüsselwörter

Pharmakodynamik - Pharmakoepidemiologie - Nebenwirkungsmechanismen - Arzneimittelsicherheit - Pharmakovigilanz

Key words

Pharmacodynamics - pharmacoepidemiology - side effect mechanisms - drug safety - pharmacovigilance

Publication History

Article published online:
27 August 2024

• Literatur

• 1 De Bruin ML, Pettersson M, Meyboom RHB. et al Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death. Eur Heart J 2005; 26: 590-597
• 2 Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM). Pharmakoepidemiologie. https://www.bfarm.de/DE/Das-BfArM/Aufgaben/Forschung/Pharmakoepidemiologie/_node.html Stand: 26.6.2024
• 3 Currie GM. Pharmacology, part 1 : Introduction to pharmacology and pharmacodynamics. J Nucl Med Technol 2018; 46: 81-86
• 4 European Medicines Agency: EudraVigilance. https://www.ema.europa.eu/en/human-regulatory-overview/research-development/pharmacovigilance-research-development/eudravigilance Stand: 26.6.2024
• 5 Faillie JL. Case–non-case studies: Principle, methods, bias and interpretation. Therapie 2019; 74: 225-232
• 6 Food and Drug Administration: FDA Adverse Event Reporting System (FAERS). https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard Stand: 26.6.2024
• 7 Fusaroli M, Giunchi V, Battini V. et al Exploring the underlying mechanisms of drug-induced impulse control disorders: a pharmacovigilance-pharmacodynamic study. Psychiatry Clin Neurosci 2023; 77: 160-167
• 8 Gahr M, Zeiss R, Lang D. et al Risk of bleeding related to selective and non-selective serotonergic antidepressants: a case/non-case approach using data from two pharmacovigilance databases. Pharmacopsychiatry 2015; 48: 19-24
• 9 Gahr M, Connemann BJ, Muche R. et al The Impact of Serotonin Transporter Binding Affinity on the Risk of Bleeding Related to Antidepressants. J Clin Psychopharmacol 2021; 41: 470-473
• 10 Garrido A, Lepailleur A, Mignani SM. et al hERG toxicity assessment: Useful guidelines for drug design. Eur. J Med Chem 2020; 195: 112290
• 11 Lapeyre-Mestre M, Montastruc F. Interest of pharmacoepidemiology for pharmacodynamics and analysis of the mechanism of action of drugs. Therapie 2019; 74: 209-214
• 12 Meyboom RHB, Egberts ACG, Edwards IR. et al Principles of signal detection in pharmacovigilance. Drug Saf 1997; 16: 355-365
• 13 Montastruc F, Palmaro A, Bagheri H. et al Role of serotonin 5-HT 2 C and histamine H 1 receptors in antipsychotic-induced diabetes: A pharmacoepidemiological-pharmacodynamic study in VigiBase. Eur Neuropsychopharmacol 2015; 25: 1556-1565
• 14 Montastruc JL, Benevent J, Montastruc F. et al What is pharmacoepidemiology? Definition, methods, interest and clinical applications. Therapie 2019; 74: 169-174
• 15 Nguyen TTH, Pariente A, Montastruc JL. et al An original pharmacoepidemiological – pharmacodynamic method: application to antipsychotic-induced movement disorders. Br J Clin Pharmacol 2017; 83: 612-622
• 16 Nguyen TTH, Roussin A, Rousseau V. et al Role of Serotonin Transporter in Antidepressant-Induced Diabetes Mellitus: A Pharmacoepidemiological – Pharmacodynamic Study in VigiBase^® . Drug Saf 2018; 41: 1087-1096
• 17 Patras de Campaigno E, Bondon-Guitton E, Laurent G. et al Identification of cellular targets involved in cardiac failure caused by PKI in oncology: an approach combining pharmacovigilance and pharmacodynamics. Br J Clin Pharmacol 2017; 83: 1544-1555
• 18 Renoux C, Vahey S, Dell’Aniello S. et al Association of Selective Serotonin Reuptake Inhibitors With the Risk for Spontaneous Intracranial Hemorrhage. JAMA Neurol 2017; 74: 173
• 19 Sekine Y, Rikihisa T, Ogata H. et al Correlations between in vitro affinity of antipsychotics to various central neurotransmitter receptors and clinical incidence of their adverse drug reactions. Eur J Clin Pharmacol 1999; 55: 583-587
• 20 Siafis S, Papazisis G. Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance-pharmacodynamic study. Br J Clin Pharmacol 2018; 84: 2405-2414
• 21 Stahl SM. Stahl’s Essential Psychopharmacology. 5th ed. Cambridge: Cambridge University Press; 2021
• 22 WHO. The Importance of Pharmacovigilance – Safety Monitoring of Medicinal Products. Genf, 2002
• 23 WHO. VigiBase. https://who-umc.org/vigibase Stand: 26.6.2024
• 24 Yung-Chi C, Prusoff WH. Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 1973; 22: 3099-3108