Integrated bioinformatic and pharmacokinetic models of high-dimensional drug interactions

Project: Research project

Project Details

Description

Project Summary
Adverse drug events are the fifth leading cause of death in the United States, lead to increased morbidity, and
are responsible for a large economic cost on the healthcare system. Polypharmacy is associated with
increased risk of adverse events. We hypothesize that individuals taking multiple medications are at an
increased risk of drug-drug interactions, leading to clinically relevant adverse events. Through a combination
of computational data mining algorithms, statistical inference, and mechanistic pharmacology models, we seek
to identify and evaluate clinically significant high dimensional drug interactions (HD-DDIs). We propose a
novel frequent close itemset mining algorithm to identify candidate HD-DDIs with adverse reactions from large
health record data sets. These HD-DDIs identified by the computational algorithm will be subjected to an
innovative empirical Bayes statistical inference to determine this false positive, hence its statistical significance
in its potential relevance of each interaction. As a large number of drug interactions are potentiated through
the cytochrome P450 (CYP450) system, the mechanistic potential of interactions among multidrug regimens
will be evaluated using in vitro metabolism assays. This innovative approach, combining graphical, statistical
inference and mechanistic pharmacology models will provide insight into the role of polypharmacy in adverse
drug events.
StatusFinished
Effective start/end date1/1/1612/31/18

Funding

  • National Institutes of Health: $367,300.00

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