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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.

Phencyclidine (PCP) has become a major drug of abuse in recent years, and treatment of PCP overdose thus becomes a major concern. This dissertation was designed to examine the pharmacokinetics of PCP in dogs and to provide a rational basis for overdose treatment. One method of treating toxicity was also tested. Before any animal studies could begin, however, analytical procedures for PCP and its metabolites had to be developed. Three gas chromatographic procedures capable of analyzing PCP, two monohydroxymetabolites (PCHP and PPC), and a pentanoic acid metabolite (PCAPA) were developed. Each assay was validated for accuracy and precision. The analytical methods for the metabolites of PCP were up to 50 times more sensitive than others previously reported in the literature. The analytical method for PCP, PCHP and PPC was also able to separate the cis and trans forms of PPC. Animal studies were performed to determine the pharmacokinetic behavior of PCP in dogs. From these experiments, PCP was determined to have a very high clearance (Cls) value approaching the upper limits of hepatic blood flow. PCP has a very large volume of distribution (V) and relatively short half-life (t(, 1/2)). The clearance of PCP was mainly due to metabolism and not to excretion of the unchanged drug. Radioactivity studies showed total recovery ranging between 65 and 80% of the dose administered. PCP was primarily metabolized to PCAPA, PCHP, and PPC. PCHP and PPC were very quickly conjugated. Bioavailability ranged between 15 and 50%. Oral clearance, an estimate of intrinsic clearance, was very large. Pharmacokinetic parameters of PPC and PCHP were similar to each other and comparable to PCP. The administration of activated charcoal increased the clearance of PCP but this increase was not statistically significant from controls.

Diss. (sammanfattning) Göteborg : Univ. , 2006. / Härtill 4 uppsatser.

Thèse (M.Ps.)--Université Laval, 2002. / Bibliogr.: f. 64-88. Publié aussi en version électronique.

Yes / Female hooded-Lister rats received either sub-chronic phencyclidine (PCP) (2 mg/kg, n=20) or vehicle (1 ml/kg, n=20) i.p. twice daily for seven days, followed by a seven-day washout period. Rats were challenged with acute PCP or vehicle and tested for locomotor activity to ensure hyperactivity was observed in the sub-chronic PCP treated rats. Rats were then tested on the elevated plus maze and in an open field for 10 minutes. Sub-chronic PCP did not significantly affect behaviour on the elevated plus maze or in the open field. In conclusion, sub-chronic PCP does not induce anxiety-like behaviour.

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Thesis (Ph.D.)--University of Wollongong, 2007. / Typescript. Includes bibliographical references: leaf 176-199.

Thèse (M.Ps.)--Université Laval, 2003. / Bibliogr.: f. 82-114. Publié aussi en version électronique.