The overall objective of this program is to conduct preclinical toxicologic and pharmacologic evaluations of new drugs, drug combinations, and new treatments prior to their development to human clinical trial. These evaluations are carried out in at least two species following the mandated guidelines of the Good Laboratory Practices Act, and the suggested guidelines of the Food and Drug Administration. The toxicologic evaluation of new treatments/drugs has 2 stated objectives; 1.) to define precisely the lethality of the new agent in a small animal species (if the agent is cytotoxic and is to be used at maximally tolerated doses for therapeutic effect in man); and 2.) to define the organ specific toxicities of the new agent/combination of agents in an appropriate large animal species. With such information a safe starting dose in man can be calculated, and information regarding the probable toxicities in man, and the means to effectively monitor these toxicities is provided to the Phase I clinician. Evaluation of toxicities in animals is carried out by extensive physical examinations and observations, serial serum chemistry and hematologic exams, and full gross and histopathologic exam on all animals. When necessary, additional testing is conducted (e.g., blood gases, lymphokine measurement, serum electrophoresis, isoenzyme analysis, immune function tests, etc.). The biodistribution and pharmacokinetics of the agents/combination of agent are studied and correlated with the toxicological picture to provide an additional measure of safety in the transfer of the agent (s) to clinical trial, and to evaluate the potential for metabolism/distribution changes when they combinations of agents are used. Toxicologic and pharmacologic profiles and the basis for selective toxicity of analogs of established agents, or of new formulations of established agents (e.g., liposome encapsulation) or of new combination treatments are also carried out prior to a decision to embark on full- scale drug development if such information is needed for that decision.
Showing the most recent 10 out of 135 publications
