Challenges and opportunities with modelling and simulation in drug discovery and drug development

Xenobiotica. 2007 Oct-Nov;37(10-11):1295-310. doi: 10.1080/00498250701534885.


The benefits of modelling and simulation at the pre-clinical stage of drug development can be realized through formal and realistic integration of data on physicochemical properties, pharmacokinetics, pharmacodynamics, formulation and safety. Such data integration and the powerful combination of physiologically based pharmacokinetic (PBPK) with pharmacokinetic-pharmacodynamic relationship (PK/PD) models provides the basis for quantitative outputs allowing comparisons across compounds and resulting in improved decision-making during the selection process. Such PBPK/PD evaluations provide crucial information on the potency and safety of drug candidates in vivo and the bridging of the PK/PD concept established during the pre-clinical phase to clinical studies. Modelling and simulation is required to address a number of key questions at the various stages of the drug-discovery and -development process. Such questions include the following. (1) What is the expected human PK profile for potential clinical candidate(s)? (2) Is this profile and its associated PD adequate for the given indication? (3) What is the optimal dosing schedule with respect to safety and efficacy? (4) Is a food effect expected? (5) How can formulation be improved and what is the potential benefit? (6) What is the expected variability and uncertainty in the predictions?

MeSH terms

  • Absorption
  • Animals
  • Biological Transport, Active
  • Drug Design*
  • Drug Interactions
  • Food
  • Humans
  • Models, Biological*
  • Xenobiotics / pharmacokinetics
  • Xenobiotics / pharmacology


  • Xenobiotics