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 language | English (US) |
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Pages (from-to) | 1-14 |
Number of pages | 14 |
Journal | Biopharmaceutics and Drug Disposition |
Volume | 35 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2014 |
Externally published | Yes |
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)