Open Systems Pharmacology
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v11
  • README
  • Open Systems Pharmacology Suite Manual & Copyright
  • How to Contribute
  • Mechanistic Modeling of Pharmacokinetics and Dynamics
    • Modeling Concepts
      • PBPK Modeling - Systems Biology
      • PK and PD Modeling
      • Principles of PBPK Modeling
      • Expression Data for PBPK Modeling
      • Modeling of Proteins
      • PD and Reaction Network Modeling
  • Open Systems Pharmacology Suite
    • Modules, Philosophy, and Building Blocks
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    • PK-Sim Documentation
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      • Creating Populations
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      • Compounds: Definition and Work Flows
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      • Simulations
      • Importing and Exporting Project Data and Models
      • Conversion of Projects from Previous Version
      • Command Line Interface - CLI
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    • MoBi‌ Documentation
      • First Steps
      • The Building Block Concept
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      • Setting up a Simulation
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      • Diagrams Overview
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  • Shared Tools and Example Workflows
    • Features of Tables
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    • Comparison of Building Blocks
    • Parameter Identification
    • Sensitivity Analysis
    • Import and Edit of Observed Data
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    • Working Journal
    • History Manager and History Reporting‌
    • Setting up a Reaction Network‌
    • Setting up a Drug-Drug Interaction in PK-Sim‌
    • Qualification‌
  • Working with R‌
    • ospsuite-R Documentation
  • Appendix
    • Appendix
    • OSP Suite Fact Sheet
  • References
    • References
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  1. Mechanistic Modeling of Pharmacokinetics and Dynamics
  2. Modeling Concepts

PK and PD Modeling

PreviousPBPK Modeling - Systems BiologyNextPrinciples of PBPK Modeling

Last updated 3 years ago

Pharmacokinetics (PK) may be defined as what the body does to the drug, as opposed to pharmacodynamics (PD) which may be defined as what the drug does to the body [].

The site of action of a pharmacological substance might be restricted to certain tissues or cells, which is why a quantitative estimate of the amount of administered substance that is available at the site of action is required. This question is the subject of pharmacokinetics and different modeling techniques are well- established in pharmaceutical research to support its investigation. So far, the most widely used approach is to establish descriptive and comparatively simple compartmental PK models that can be well identified based on available data. Often these models are applied to population PK data using nonlinear mixed-effect techniques (NLME), e.g. to quantify sources of population variability or covariate effects. Besides PK, such models may also include a description of a compound's effects (PD), for example, in the form of a simple hyperbolic or sigmoid concentration-effect relation (Michaelis-Menten, Hill, or Emax type).

In classical pharmacokinetic modeling, the aim is to fit a comparatively simple model to experimental data in order to determine pharmacokinetic parameters from the fitted concentration-time-course. These parameters are used to characterize and quantify the behavior of the investigated substance in general or in a certain clinical trial and, potentially, to make extrapolations to situations that have not been already investigated.

In contrast to the rather phenomenological consideration of drug PK in compartmental models, physiologically–based pharmacokinetic (PBPK) models aim for a detailed representation of physiological processes as will be summarized in the following. Consequently, PBPK-modeling is based on the mathematical description of physical and physiological processes and in the framework of PBPK modeling a genuine simulation of the pharmacokinetic behavior using this description is performed. Also, the pharmacodynamics can be represented in more mechanistic detail as briefly discussed in . A good starting point for further reading can be found in [].

Modeling Concepts - PD and Reaction Network Modeling
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Structure of compartmental PK model (A) and PBPK model (B)