ADRs are a major cause of hospitalization and a large cost burden to healthcare systems. A further complicating factor is that many ADRs are rare, but serious, events, dependent on factors such as metabolic state, drug-drug interactions (DDIs) and pharmacogenetic variation within the patient population. We have applied a simple systems-based theoretical model of poly-/network-pharmacology and PK/PD models, combined with a data-mining approach, to the generation of a new strategy to identify drug combinations that have improved safety profiles. This drug combination approach is also theoretically predicted to reduce intra-patient pharmacogenetic-based differences in drug response/efficacy, as an additional emergent property. The theoretical basis for this approach will be outlined, along with representative examples of specific drug combinations with synergistic safety features. Finally, we outline our plans to test this hypothesis across a variety of cardiovascular diseases.

Drug combinations to reduce adverse drug reactions and improve intrapatient differences in response

243rd National Meeting (2012)

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