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Clinical Pharmacology & Therapeutics
Article . 2024 . Peer-reviewed
License: CC BY NC ND
Data sources: Crossref
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https://doi.org/10.1101/2023.1...
Article . 2023 . Peer-reviewed
Data sources: Crossref
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Phenotypic Models of Drug–Drug‐Gene Interactions Mediated by Cytochrome Drug‐Metabolizing Enzymes

Authors: Roberto Viviani; Judith Berres; Julia C. Stingl;

Phenotypic Models of Drug–Drug‐Gene Interactions Mediated by Cytochrome Drug‐Metabolizing Enzymes

Abstract

Genetic polymorphisms in drug metabolizing enzymes and drug–drug interactions are major sources of inadequate drug exposure and ensuing adverse effects or insufficient responses. The current challenge in assessing drug–drug gene interactions (DDGIs) for the development of precise dose adjustment recommendation systems is to take into account both simultaneously. Here, we analyze the static models of DDGI from in vivo data and focus on the concept of phenoconversion to model inhibition and genetic polymorphisms jointly. These models are applicable to datasets where pharmacokinetic information is missing and are being used in clinical support systems and consensus dose adjustment guidelines. We show that all such models can be handled by the same formal framework, and that models that differ at first sight are all versions of the same linear phenoconversion model. This model includes the linear pharmacogenetic and inhibition models as special cases. We highlight present challenges in this endeavor and the open issues for future research in developing DDGI models for recommendation systems.

Country
Germany
Keywords

Phenotype, Polymorphism, Genetic, Pharmaceutical Preparations, Cytochrome P-450 Enzyme System, Pharmacogenetics, Humans, Drug Interactions, Models, Biological

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    11
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
11
Top 10%
Average
Top 10%
Green
hybrid