3.6. Physiological Based Models
The compartmental models do not give any information about the drug concentrations in specific organs, and are not amenable to transfer from one species to another. To provide some insight into these areas, some investigators have used a physiological model, in which specific organs and tissues of the body are modeled as individual compartments. An example is outlined figure 3.6.1.
The model then uses actual blood flow rates through the specific organ, together with and rates of diffusion of the drug into, and relative affinities of the drug between, the organ and the plasma. Some examples of blood flow through organs are given in the class notes, and they range form a high of 1500 mL/min in the liver to a low of 250 mL/min in the muscles of the heart. The liver is a highly vascular organ, and since it is the detoxifying site of the body, a high blood flow rate is expected.
Some of the advantages of the physiological model include the more realistic nature of the derived parameters, the ability to change parameters to allow for physiological changes, the ability to predict drug concentrations, and elimination mechanisms for specific organs, and the ability to scale values from one species to another. These advantages are gained at the expense of a far more complicated mathematical treatment, a need for a huge data base for each drug, difficulties of obtaining tissue samples from human subjects, and the possibility of erroneous simplifying assumptions. As a result this approach has only been tried for a few drugs.
Figure 3.6.1. An example of a comprehensive physiologically based pharmacokinetic model flow scheme after Jain et al. Annals of Biochemical engineering vol. 9 (1982 pp 347-361).