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    Pharmacometabolomics of clopidogrel: Determining the genetic and metabolic contributors to clopidogrel response

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    Author
    Bromberek, Sarah Katherine
    Advisor
    Beitelshees, Amber L.
    Date
    2021
    Type
    dissertation
    
    Metadata
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    Abstract
    Clopidogrel is a commonly prescribed antiplatelet drug and there is considerable variability in response. The PAPI study was conducted in 687 individuals to determine the genetic predictors of clopidogrel response. Targeted metabolomic profiling of 42 amines was performed in a subset of 198 PAPI subjects with genetics data available. We identified the metabolic signature of clopidogrel and determined metabolites associated with clopidogrel-induced changes in platelet reactivity. We found tyrosine was most significantly changed after exposure to clopidogrel, and BCAAs baseline levels were associated with clopidogrel-induced changes in platelet aggregation. Gaining insights into factors that influence variability in antiplatelet response is important for identifying novel antiplatelet mechanisms or biomarkers for predicting response. These findings can have long-term implications toward advancing precision medicine in antiplatelet therapy.
    Description
    University of Maryland, Baltimore. Human Genetics. M.S. 2021.
    Keyword
    pharmacometabolomics
    Clopidogrel--metabolism
    Platelet Aggregation Inhibitors
    Tyrosine
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/19304
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    Theses and Dissertations School of Medicine
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