Abstract
Clinical pharmacology is a broad professional and scientific discipline concerned with all aspects of drug use in humans. One of the primary goals of this field is to improve health outcomes by supporting the development, rational use, and safety of medicines. Clinical pharmacology and pharmacometrics are closely related and share common goals and research themes. Notable amongst these are pharmacokinetics and pharmacodynamics. In the pharmaceutical industry, population pharmacokinetic and pharmacokinetic-pharmacodynamic studies aid dose selection, assess links between drug exposure and efficacy and safety metrics, and inform the dosing information that will be presented on the drug label. In the clinical environment, population pharmacokinetic and pharmacokinetic-pharmacodynamic studies are conducted to aid dose optimization for an individual patient. The aim of this chapter is to present an overview of population pharmacokinetic and pharmacokinetic-pharmacodynamic concepts and methodology as they apply in the industrial and clinical setting. The chapter is divided into four parts: Part 1 will provide a board overview of general concepts and definitions related to population pharmacokinetic and pharmacokinetic-pharmacodynamic analyses, Part 2 will look at commonly used models, Part 3 will explore methodology, primarily nonlinear mixed effects modeling, and Part 4 will present examples of pharmacokinetic and pharmackinetic-pharmacodynamic analyses, presented in the style that is typical for a regulatory submission involving phase I data.
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Wright, D.F.B., Hasegawa, C., Al-Sallami, H.S. (2018). Population Pharmacokinetics and Pharmacokinetic-Pharmacodynamics in Clinical Pharmacology. In: Hock, F., Gralinski, M. (eds) Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer, Cham. https://doi.org/10.1007/978-3-319-56637-5_18-1
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DOI: https://doi.org/10.1007/978-3-319-56637-5_18-1
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