A simple index for representing the discrepancy between simulations of physiological pharmacokinetic models and experimental data.

The objective of this study was to develop an index that would provide a quantitative measure of the degree of discrepancy between simulations of physiologically based pharmacokinetic (PBPK) models and experimental data. The approach we developed involves the calculation of the root mean square of the error (representing the difference between the individual simulated and experimental values for each sampling point in a time course curve), and dividing it by the root mean square of the experimental values. The resulting numerical values of discrepancy measures for several data sets (each corresponding to an end point) obtained in a single experimental study are then combined on the basis of a weighting proportional to the number of data points contained in each data set. Such consolidated discrepancy indices obtained from several experiments (e.g., exposure scenarios, doses, routes, species) are averaged to get an overall discrepancy index, referred to as the PBPK index. This empirical index reflects the overall, weighted average percent difference between the a priori PBPK model simulations and experimental data. The proposed methodology is illustrated using previously published experimental and simulated data on dichloromethane pharmacokinetics in humans. The application of this kind of a "quantitative" method should help remove the ambiguity in communicating the degree of concordance or discrepancy between PBPK model simulations and experimental data.