Population pharmacokinetics interoccasion variability

Karlsson, M. O., Sheiner, L. B. The importance of modeling interoccasion variability in population pharmacokinetic analyses. 

The objective for performing a population pharmacokinetic study should be taken into consideration in designing such a study. When designing a population pharmacokinetic study, the practical limitations of sampling times, number of samples/subject, and number of subjects should be considered. Also, the sampling of subjects at various periods (study days) should be considered if interoccasion variability is... 

Nonlinear mixed effects models are similar to linear mixed effects models with the difference being that the function under consideration f(x, 0) is nonlinear in the model parameters 0. Population pharmacokinetics (PopPK) is the study of pharmacokinetics in the population of interest and instead of modeling data from each individual separately, data from all individuals are modeled simultaneously. To account for the different levels of variability (between-subject, within-subject, interoccasion, residual, etc.), nonlinear mixed effects models are used. For the remainder of the chapter, the term PopPK will be used synonymously with nonlinear mixed effects models, even though the latter covers a richer class of models and data types. Along with PopPK is population pharmacodynamics (PopPD), which is the study of a drug s effect in the population of interest. Often PopPK and PopPD are combined into a singular PopPK-PD analysis. 

In a population analysis, there are usually two sources of variability between-subject variability (BSV), sometimes called intersubject variability, and residual variability. Between-subject variability refers to the variance of a parameter across different individuals in the population. In this text, intersubject variability will be used interchangeably with between-subject variability. Residual variability refers to the unexplained variability in the observed data after controlling for other sources of variability. There are other sources of variability that are sometimes encountered in the pharmacokinetic literature interoccasion variability (IOV) and interstudy variability. Each of these sources of variability and how to model them will now be discussed. 

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