Integration of Genome Scale Metabolic Networks and Gene Regulation of Metabolic Enzymes With Physiologically Based Pharmacokinetics

CPT Pharmacometrics Syst Pharmacol. 2017 Nov;6(11):732-746. doi: 10.1002/psp4.12230. Epub 2017 Sep 8.

Abstract

The scope of physiologically based pharmacokinetic (PBPK) modeling can be expanded by assimilation of the mechanistic models of intracellular processes from systems biology field. The genome scale metabolic networks (GSMNs) represent a whole set of metabolic enzymes expressed in human tissues. Dynamic models of the gene regulation of key drug metabolism enzymes are available. Here, we introduce GSMNs and review ongoing work on integration of PBPK, GSMNs, and metabolic gene regulation. We demonstrate example models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computer Simulation
  • Gene Expression Regulation*
  • Genome, Human
  • Humans
  • Metabolic Clearance Rate
  • Metabolic Networks and Pathways*
  • Models, Biological
  • Pharmacokinetics