Physiologically-based pharmacokinetic (PB-PK) model or modeling was mentioned several times in this lecture (e.g., Slides 12 - 15) and in the previous two. It is perhaps to the point that such an overselling without some actual description of this modeling has become rather annoying to the students. Thus here a brief description of PB-PK model seems to be in order.

Basic to each of the PB-PK models is a set of mathematical (differential) equations which are structured to offer presumably a fairly comprehensive time course of a chemical’s mass-balance disposition in several pre-selected anatomical compartments (e.g., skin, fat tissue, liver, gastrointestinal tract, kidney, muscle, lung, etc.). Each of these compartments has its unique characteristic blood flow, volume, tissue-blood partition coefficient, and metabolic clearance rate constants that together are deemed responsible for a chemical’s disposition in that region (Dong, 1994).

Some of the input data or values for a PB-PK model are more easy to obtain, such as tissue volume, the cardiac output, and the blood flow to a particular tissue. Others, such as the partition coefficient between a particular tissue and the blood, are chemical-specific and hence are not always readily available. Because the differential equations used cannot be integrated directly, they have to be solved indiscriminately with numerical procedures (e.g., the Runge-Kutta method) written for the approximation of an analytical solution (Dong, 1994). Such an integration approximation can be accomplished only through laborious as well as intensive iterations with a computer program.