Modeling Kinetics of Subcellular Disposition of Chemicals

Theoretical fundamentals, status, applications to experimental data, and probable future development trends of structure-based subcellular pharmacokinetics (SBSP), are reviewed. The SBSP models are common mass-action based models for the interactions of chemicals with body constituents, which are placed within the framework of intracellular and extracellular compartments separated by membranes. Transcytosis, the transfer of ligands through the epithelial cell, with relocation of the caveolae to the opposite surface, is documented for plasma proteins including albumin and transthyretin. The size of the algae cells has allowed a direct chemical analysis of the cellular content, while a similar analysis of cellular content is applied to the protoplasts of oyster plant. A proper application of the SBSP concepts to the chemical disposition in organisms results in expressions that provide similar time dependencies as the compartmental equations of classical pharmacokinetics.