Chapter 22

Pharmacodynamic Models and
Physiologically Based Pharmacokinetic Models

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Student Objectives for this Chapter

• To understand the different types of concentration - effect relationships
• To understand the mathematical relationships involved with direct reversible pharmacological effect kinetics
• To understand the development and use of physiologically based pharmacokinetic (PBPK) models

Figure 22.1.1 Diagram Representing Model Links between Data and Applications

The method of data analysis or modeling should match the data available and potential applications of the data and models. Compartmental models allow summarization of data and understanding of drug processes and the calculation of dose regimens and doses to effective drug concentrations. Model independent analysis allows summarization of data but reduced understanding of the time or dose dependent processes. Calculation of dosage regimens to an effective drug concentration is possible. Physiologically based and pharmacodynamic models require more data but allow increased understanding of drug distribution and response. These models allow dose adjustment to target tissue concentration or to a required drug response.

Figure 22.1.2 Diagram Representing Model Extension with More Data

With more data, more samples or sampling sites, the models can be expanded or extended. Drug concentrations in various tissues allows the understanding and quantization of drug distribution in more detail. Drug response, either therapeutic or toxic, can be incorporated into useful models. Patient covariate information provides information for customizing dosing regimens to a particular patient.

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