PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODELS - EXAMPLES OF THEIR USE IN EXPOSURE AND RISK ASSESSMENT

Pharmacokinetics describes the time course disposition of a xenobiotic, its biotransformed products, and its interactive products within the body. It includes a description of the compounds's absorption across the portals of entry, transport and distribution throughout the body, biotransformation by metabolic processes, interaction with biomolecules, and eventual elimination from the body. Pharmacokinetic (PK) analyses or assessments can be used in two very general ways. First, they can be applied for forward analysis. Such PK analyses use exposure data to calculate biologically meaningful measures of dose. Second, they can be applied for reconstructive dose assessment. In this case, data on measured biomarkers or tissue concentrations of a compound and/or its metabolites are used to calculate total dose of a xenobiotic received by an organism. This paper will focus on general concepts of model structure, examples of their use and examples of the use of models for analysis of biomarker data.