[Compartment simulation models and physiologic use in pharmaco- and toxicokinetics]

Abstract

The pharmaco- and toxicokinetic studies describe the process of absorption, distribution, metabolism and elimination of drugs or chemical compounds in animals and humans. In simple compartmental models, the body is divided into basic compartments, central and peripheral. The central compartment is an equilibrium of arterial and venous blood flows, and the peripheral one is connected to the central compartment through a series of flow rate constants that describe the flow of chemicals in both directions. For instance, we can use the PH/EDSIM software for calculating the constants. The flow of the material from one to the other reflected by vectorial connections of two types of kinetics: linear and Michaelis-Menten (nonlinear). At present, the PB-PK models (physiologically-based pharmacokinetic models), which rely on actual physiological (breath rates, blood flow rates and tissue volumes), biochemical and metabolic parameters, tend to be more commonly used. Tissue groups or compartments that are frequently applied in PB-TK model include organs, muscle, fat tissue and the liver. Tissue compartments are connected by arterial and venous blood flows, and each compartment is characterised by a unique set of differential equations. The flow rate constants that describe that flow of materials from and to the compartments, and the rate of change in the amount of chemical in each compartments are directly proportional to the blood flow rate, tissue solubility and organ value.