Pharmacokinetic (PK) studies aim to develop models of the absorption, distribution, metabolism and excretion of a drug by the body. Traditional PK studies focus on minimizing inter-individual variability and obtaining initial understandings of the PK pathways, often through use of a sample of healthy subjects and strict study control protocols. In contrast, population-PK studies typically utilize a large sample from the population of interest and attempt to explain sources of variability

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... ng various demographic, genetic, or concomitant drug covariates. PK studies represent a significant step in the drug development process and inform dosing regimens, minimize toxicity, and increase drug efficacy. Drug PK may be understood as a series of compartments where organs or tissues grouped within a compartment have similar absorption and/or elimination rates. When equilibrium is quickly achieved across tissues a one-compartment model is sufficient. More often, a two-or more compartments model may be required. Each compartmental model has associated PK parameters; for instance 1 1 for absorption rate, 11 for clearance, and I for volume. Because multiple measurements are taken per individual, nonlinear mixed effects models present a means to model PK parameters, account for repeated measurements, and adjust for potential covariates on each PK parameter explicitly. NONMEM, a commercially-available software, is specifically designed to analyze these types of models.