Phencyclidine disposition and reversal of toxicity by monoclonal antibody.

Persistent Link:
http://hdl.handle.net/10150/184637
Title:
Phencyclidine disposition and reversal of toxicity by monoclonal antibody.
Author:
Bozigian, Haig Philip.
Issue Date:
1989
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
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.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Monoclonal antibodies.; Phencyclidine -- Toxicology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmaceutical Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Mayersohn, Michael

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titlePhencyclidine disposition and reversal of toxicity by monoclonal antibody.en_US
dc.creatorBozigian, Haig Philip.en_US
dc.contributor.authorBozigian, Haig Philip.en_US
dc.date.issued1989en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractA 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.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectMonoclonal antibodies.en_US
dc.subjectPhencyclidine -- Toxicology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmaceutical Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMayersohn, Michaelen_US
dc.contributor.committeememberKarol, Michaelen_US
dc.contributor.committeememberYalkowsky, Samuelen_US
dc.contributor.committeememberFriedman, Richarden_US
dc.contributor.committeememberMeinke, Geraldineen_US
dc.identifier.proquest8915948en_US
dc.identifier.oclc702148257en_US
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