A physiologic model for phencyclidine disposition in the rat was established. This model was able to accurately predict phencyclidine disposition in most rat tissues. Physiologic models are based on actual physiologic, anatomic, and biochemical considerations. As a result, these models can be used to predict drug disposition under conditions of altered physiology or anatomy. This aspect of physiologic modeling was tested in the present study by examining the ability of the model to predict phencyclidine plasma disposition in dog and man. The model developed in this study was able to accurately predict phencyclidine disposition in these species. A primary goal of this project was to evaluate the effects of the administration of an anti-phencyclidine monoclonal antibody on phencyclidine disposition and toxicity in the rat. The monoclonal antibody was produced in murine ascites fluid. The antibody was purified using a recirculating isoelectric focusing apparatus. This method provided a rapid technique which can be used to purify monoclonal antibody from large quantities of ascites fluid, yielding reasonably good antibody recovery and very high purity. Characterization of the antibody showed only moderate affinity and high cross reactivity. Administration of the monoclonal antibody did not significantly alter either phencyclidine disposition or toxicity. While qualitative differences in recovery from phencyclidine-induced toxicity occurred in rats receiving the anti-phencyclidine antibody, these differences failed to be statistically different from control rats. These results may be explained by the poor qualities (moderate affinity, high cross-reactivity) of the monoclonal antibody.

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