Population Pharmacokinetics

Population Pharmacokinetics (or more generally, nonlinear mixed effect modeling) can be defined as the study of the sources of variability in drug concentrations among individuals who represent the target population that ultimately receives relevant doses of the drug of interest. [1]

Population Pharmacokinetics (or more generally, nonlinear mixed effect modeling) is not limited to just pharmacokinetic studies and may include pharmacodynamic or toxicokinetic studies.

 
 
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Population pharmacokinetics seeks to identify the measurable pathophysiologic factors that cause changes in the dose-concentration relationship and the extent of these changes so that, if such changes are associated with clinically significant shifts in the therapeutic index, dosage can be appropriately modified.

The settings in which population pharmacokinetics can be employed vary greatly and span all phases of drug development from drug discovery through Phase 4.

In contrast to traditional pharmacokinetic evaluation, the population PK approach encompasses some or all of the following features[2]:

  • The collection of relevant pharmacokinetic information in patients who are representative of the target population to be treated with the drug.

  • The identification and measurement of variability during drug development and evaluation.

  • The explanation of variability by identifying factors of demographic, pathophysiological, environmental, or concomitant drug-related origin that may influence the pharmacokinetic behavior of a drug.

  • The quantitative estimation of the magnitude of the unexplained variability in the patient population.

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The magnitude of the unexplained (random) variability is important because the efficacy and safety of a drug may decrease as unexplainable variability increases.  

Knowledge of the relationship among concentration, response, and physiology is essential to the design of dosing strategies for rational therapeutics that may not necessarily require therapeutic drug monitoring. [Guidance for Industry: Population Pharmacokinetics by the Food and Drug Administration]

  1. Barrett, J.S., “Population Pharmacokinetics” (Chapter 15) in Schoenwald, R. D. (Ed.), Pharmacokinetics in Drug Discovery and Development (315-356). CRC Press, 2002.

  2. Steimer, J. L., S. Vozeh, A. Racine-Poon, et al., "The Population Approach: Rationale, Methods, and Applications in Clinical Pharmacology and Drug Development" (Chapter 15), in Welling, P. G. and L. P., Balant (eds.), Pharmacokinetics of Drugs (Handbook of Experimental Pharmacology), Berlin-Heidelberg: Springer-Verlag. Vol 110:404-451, 1994.