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  • Quantitatively describe the relationship between drug, receptor, and the pharmacologic response.

  • Explain why the intensity of the pharmacologic response increases with drug concentrations and/or dose up to a maximum response.

  • Explain the difference between an agonist, a partial agonist, and an antagonist.

  • Describe the difference between a reversible and a non-reversible pharmacologic response.

  • Define the term biomarker and explain how biomarkers can be used in the clinical development of drugs.

  • Show how the Emax and sigmoidal Emax model describe the relationship of the pharmacodynamic response to drug concentration.

  • Define the term pharmacokinetic–pharmacodynamic model and provide an equation that quantitatively simulates the time course of drug action.

  • Explain the effect compartment in the pharmacodynamic model and name the underlying assumptions.

  • Describe the effect of changing drug dose and/or drug elimination half-life on the duration of drug response.

  • Describe how observed drug tolerance or unusual hysteresis-type drug response can be explained using PD models based on simple drug receptor theory.

  • Define the term drug exposure and explain how drug exposure relates to drug therapy


The role of pharmacokinetics (PK) to derive dosing regimens to achieve therapeutic drug concentrations for optimal safety and efficacy was described in the previous chapters. A rational approach for designing a drug’s dosing regimen would be to link the exposure of the drug within the body to the desirable (efficacy) and undesirable (safety/toxicity) effects of the drug. At the site of action, the drug interacts with a receptor, and this drug−receptor interaction initiates a cascade of events resulting in a pharmacodynamic response or effect. Thus, pharmacodynamics (PD) refers to the relationship between drug concentration at the site of action (receptor) and the observed pharmacologic response. This chapter describes how the exposures of a drug over time (dose, concentrations, dosing regimens) can be related to the desirable and undesirable effects of the drug. Just as the PK of a drug has been described via mathematical models, the relationship between drug concentration and pharmacological effect can be described using mathematical models, which can be applied for simulations and predictions. The chapter is organized as follows: first, a definition of terms that are often used interchangeably in the pharmacodynamic-pharmacokinetic (PK–PD) literature is provided. Second, the reader is introduced to how the PK–PD information is integrated in drug development. Third, the chapter briefly describes the drug−receptor theory and the use of biomarkers, followed by the theoretical basis of PK–PD relationship. Lastly, the chapter describes the different types of possible PK–PD relationships with real examples. The examples and case studies provided in the chapter integrate the concepts from a drug development perspective.

Definitions for Exposure, Response, and Effect

In the study of PK and PD, it is important to use correct terminology, as terms are often used interchangeably and incorrectly. This section provides definitions of the terms that will be used throughout ...

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