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SPECIFIC AND SPECIAL POPULATIONS

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The biggest issue in PK/PD and drug therapy is variability in response.* Variability factors that affect pharmacokinetics and pharmacodynamics influence clinical trials and dose regimen designs. Early in drug development, the term “pharmacokinetics in disease states” was used to describe disease factors that affect PK. This term is concise but proved inadequate in the regulatory and clinical environment. The term “population” pharmacokinetics was then used to emphasize that the PD response can be quite different dependent on the demographic of the subjects. In the clinical trial and labeling environment, the term “specific populations” may be used to convey important specific medical conditions such as cancer or other pathophysiologic conditions that greatly influence the patient’s outcome. The terms “specific” and “special” have been used in different occasions referring to different subject populations or patient conditions.

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A population approach refers to the many factors that influence PK/PD as both intrinsic and extrinsic. Some of these factors were also discussed in Chapter 22. For example, PK differences in systemic exposure as a result of changes in age, gender, racial, weight, height, disease, genetic polymorphism, and organ impairment are well known clinically. These influences may be summarized as intrinsic factors.

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Extrinsic factors summarize information associated with the patient environment. Extrinsic factors are quite numerous and diverse. Details are discussed in International Conference on Harmonisation (ICH–E5, http://ich.org/) for clinical trials and evaluations. Some examples that are referenced in this guidance include the medical environment, use of other drugs (interaction), tobacco, alcohol, and food habits.

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The term “specific populations” in this chapter is conveniently chosen to refer to populations that have important differences in pharmacokinetics due to age (pediatric, young adult, and elderly patients) or weight (obesity). Additional alterations in pharmacokinetics may occur due to renal impairment, hepatic impairment (Chapter 24), pregnancy, various pathophysiologic conditions, and drug–drug interactions discussed elsewhere.

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This chapter focuses on three specific populations, which are divided into the following modules:

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  • Module I Application of Pharmacokinetics to the Geriatric Patients

  • Module II Application of Pharmacokinetics to the Obese Patients

  • Modula III Application of Pharmacokinetics to the Pediatric Patients

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*Disclaimer: The geriatric section of this chapter reflects the views and opinions of this author and does not represent the views and opinions of the Food and Drug Administration. This author declares no conflict of interest.

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MODULE I: APPLICATION OF PHARMACOKINETICS TO THE GERIATRIC PATIENTS

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Objectives

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  • List the demographic changes in the coming decades.

  • Describe the effects of age on pharmacokinetics in older adults.

  • Describe the effects of age on pharmacodynamics in older adults.

  • Describe the confounders of pharmacokinetics and pharmacodynamics in older adults.

  • Describe the emerging approaches to avoid adverse drug events in older adults.

  • Describe the measures to help older adults adhere to taking their ...

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