ABSTRACT
This chapter provides the reader with a working understanding of the critical toxicokinetic (TK) parameters, how they are derived and applied, and what they mean. It introduces TK parameters as those calculated for a molecule or metabolite after high dosages in a toxicology study, ignoring the characterization of the molecule's biological activity. The chapter also plasma concentrations, recognizing that serum and rarely whole blood concentrations can be measured and used in the calculations, and the authors assume that the calculation of the TK parameters is by noncompartmental analysis. While half-life is the most visible parameter associated with the terminal phase of drug elimination, it is often the most misunderstood PK or TK parameter. Transporters and their effects on the disposition of drugs in the brain have been reviewed extensively. Although most lipophilic, low-molecular-weight drugs are absorbed transcellularly, absorption may also occur paracellularly, through the tight junctions between epithelial cells.
