UNCERTAINTIES IN PHARMACOKINETIC MODELING FOR PERCHLOROETHYLENE .2. COMPARISON OF MODEL PREDICTIONS WITH DATA FOR A VARIETY OF DIFFERENT PARAMETERS

In this paper we compare expectations derived from 10 different human physiologically based pharmacokinetic models for perchloroethylene wit h data on absorption via inhalation, and concentrations in alveolar ai r and venous blood. Our most interesting finding is that essentially a ll of the models show a time pattern of departures of predictions of a ir and blood levels relative to experimental data that might be correc ted by more sophisticated model structures incorporating either (a) he terogeneity of the fat compartment (with respect to either perfusion o r partition coefficients or both) or (b) intertissue diffusion of perc hloroethylene between the fat and muscle/VRG groups. Similar types of corrections have recently been proposed to reduce analogous anomalies in the fits of pharmacokinetic models to the data for several volatile anesthetics.(17-20) A second finding is that models incorporating res ting values for alveolar ventilation in the region of 5.4 L/min seemed to be most compatible with the most reliable set of perchloroethylene uptake data.