Abstract
Computer simulations are extremely useful for evaluating the safety of chemicals and environmental pollutants. Since such simulations can require extensive knowledge of both mathematics and computer programming, however, they are not widely used. To make such computer simulations available to more researchers, the author has developed a Pharmacokinetics Predicting Program (PPP). This program runs under Microsoft Windows and makes it possible to easily determine the tissue distribution curve for chemical substances without requiring the user to deal with differential equations or computer programming. PPP requires only that the user enter the physiological data, the pharmacokinetic parameters, and the conditions under which the chemical substance was administered. The program then predicts in vivo tissue distribution and provides graphs of the predicted pharmacokinetic results. Some environmental pollutants and chemicals become more toxic or express activity following in vivo metabolism. Thus, the development of a computer simulation program was undertaken for predicting the tissue distribution of metabolites produced via complex metabolic pathways (A→B→C...), which would utilize a physiologically based pharmacokinetic (PBPK) model. Results indicate that the peak in tissue concentration is delayed for relatively late-forming metabolites such as metabolite C. This means that, when studying toxic metabolites, we need to consider time-lag in the expression of toxicity. PPP also has potential applications in numerous other areas, including the extrapolation of animal studies to humans, planning for animal testing, and planning for individualized drug treatment.
