2-FUN

PBPK modelling tools

1. Toxicokinetic models: definition

Toxicokinetic models describe the fate of chemicals in the body of animals. Processes of absorption, distribution, metabolism and excretion basically govern that fate. Two types of compartmental toxicokinetic models are used to represent these processes: "classical" models and "physiologically-based" models.

• absorption
• distribution
• metabolism
• elimination.

2. "Classical" toxicokinetic models

Classical models describe the body as a set of interconnected compartments, without a priori anatomical basis. The number of compartments used is the minimum required to fit the toxicokinetic data available. The next figure shows a two-compartment model. Each arrow represents an exchange of chemical between compartment of to and from the outside of the body. These models can have closed-form (analytical) solutions, or can, be computed by numerical integration of a system of mass-balance differential equations.

3. "Physiologically-based" toxicokinetic (PBTK) models

PBPK models try to rely a priori on the anatomical and physiological structure of the body. These are usually also compartmental models, but the compartments correspond to predefined organs or tissues, for which the interconnections correspond to blood or lymph flows (more rarely to diffusions). A system of differential equations can still be written, but its parameters represent blood flows, pulmonary ventilation rate, organ volumes etc., for which information is available in scientific publications. Indeed the description of the body is simplified and a balance needs to be struck between complexity and simplicity. Besides the advantage of allowing the recruitment of a priori information about parameter values, these models also facilitate inter-species transpositions or extrapolation from one mode of administration to another (e.g., inhalation to oral).

Software tool to download: GNU MCSim (see the project page or the GNU project repository - the latest code source for programmers.)

Examples of GNU MCSim models and input files:

• Generic PBPK model of the man,
• Generic PBPK model of the woman,
  
• Generic PBPK model of the pregnant woman,
  
• A 5-compartment model for styrene, with an example of input file

More info on PBPK models from wikipedia.

For assistance on this topic contact Prof. Dr. Frederic Y. Bois.