Physiologically-Based Pharmacokinetic Modeling*

Physiologically-based pharmacokinetic (PB-PK) models attempt to provide both a realistic anatomic description of the animal to which a drug or toxic chemical has been administered and a biologically accurate representation of the physiological pathways for chemical storage, metabolism, and elimination in the animal. Because these models explicitly incorporate information about the biological factors which affect chemical disposition, they are particularly useful for high- to low-dose and interspecies extrapolation of pharmacokinetics. The complexity of any particular PB-PK model depends on the chemical studied and the objectives underlying model development. The primary focus of this brief overview is the structure of PB-PK models developed for three specific classes of chemicals: volatile organic compounds (VOCs), dioxin-like chlorinated aromatic hydrocarbons, and retinoids. In addition, the risk assessment objectives underpinning model development and the continuing data needs in refining and extending these models are briefly discussed.