Systems pharmacology modeling: An approach to improving drug safety

Jane P.F. Bai, Robert J. Fontana, Nathan D. Price, Vineet Sangar

Research output: Contribution to journalReview articlepeer-review

Abstract

Advances in systems biology in conjunction with the expansion in knowledge of drug effects and diseases present an unprecedented opportunity to extend traditional pharmacokinetic and pharmacodynamic modeling/analysis to conduct systems pharmacology modeling. Many drugs that cause liver injury and myopathies have been studied extensively. Mitochondrion-centric systems pharmacology modeling is important since drug toxicity across a large number of pharmacological classes converges to mitochondrial injury and death. Approaches to systems pharmacology modeling of drug effects need to consider drug exposure, organelle and cellular phenotypes across all key cell types of human organs, organ-specific clinical biomarkers/phenotypes, gene-drug interaction and immune responses. Systems modeling approaches, that leverage the knowledge base constructed from curating a selected list of drugs across a wide range of pharmacological classes, will provide a critically needed blueprint for making informed decisions to reduce the rate of attrition for drugs in development and increase the number of drugs with an acceptable benefit/risk ratio.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalBiopharmaceutics and Drug Disposition
Volume35
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

Keywords

  • biomarkers/clinical phenotype
  • cellular phenotype
  • gene drug interaction
  • mitochondria
  • molecular networks
  • molecular pathways
  • organ injury
  • systems biology

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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