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The quantitative impact of metabolism-inhibiting drugs on the occurrence of adverse drug reactions - a backward selection approach

Aim: The quantitative effect of several inhibitory drugs on the development of adverse drug reactions (ADRs) is currently difficult to estimate. Our aim was to identify metabolic pathways, which, when inhibited, increase the risk for certain ADRs, and to use this system to consider comedication at i...

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Hauptverfasser: Berres, Judith (Verfasst von) , Wozniak, Justyna (Verfasst von) , Fölsch, Hannah (Verfasst von) , Knueppel-Ruppert, Anja (Verfasst von) , Graeff, Verena (Verfasst von) , Kriegisch-Stumpf, Andrea (Verfasst von) , Dormann, Harald (Verfasst von) , Stingl, Julia (Verfasst von) , Just, Katja S. (Verfasst von)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 20 February 2026
In: British journal of clinical pharmacology
Year: 2026, Jahrgang: 92, Heft: 7, Pages: 2203-2211
ISSN:1365-2125
DOI:10.1002/bcp.70494
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/bcp.70494
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/bcp.70494
Volltext
Verfasserangaben:Judith Berres, Justyna Wozniak, Hannah Fölsch, Anja Knueppel-Ruppert, Verena Graeff, Andrea Kriegisch-Stumpf, Harald Dormann, Julia C. Stingl, Katja S. Just
Beschreibung
Zusammenfassung:Aim: The quantitative effect of several inhibitory drugs on the development of adverse drug reactions (ADRs) is currently difficult to estimate. Our aim was to identify metabolic pathways, which, when inhibited, increase the risk for certain ADRs, and to use this system to consider comedication at individual level. Methods: Data of a prospective multicentre cohort of ADRs on emergency department admissions were used (ADRED-study, trial registration: DRKS00008979). A score system to rate the burden of inhibition on pathways was implemented to calculate individual burdens per patient. These cumulative burden scores were used as predictors in binary logistic regressions to identify pathways, which were significantly positively correlated with the ADRs falls and haemorrhages, respectively. Results: Regarding falls, CYP2D6, OCT2 and carboxylesterase 1 were identified as relevant metabolic pathways with cumulative inhibitory burden. Concerning haemorrhages, CYP2C19, CYP3A4, MRP4, OAT2, OATP1B1 and carboxylesterase 1 were determined. Within relevant pathways for the occurrence of falls, common fall-risk-increasing drugs (FRIDs) and associated drugs were found, as well as bleeding inducing drugs within relevant pathways for the occurrence of haemorrhages. Conclusion: Our approach identifies plausible inhibited pathways, raising awareness that a high burden of pathway inhibition can contribute to the occurrence of ADRs. Further validation in a second dataset is necessary.
Beschreibung:Gesehen am 25.03.2026
Beschreibung:Online Resource
ISSN:1365-2125
DOI:10.1002/bcp.70494

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