The purpose of Core I will be to provide a centralized unit to facilitate pharmacological and analytical studies of AIDS-related clinical and basic science research at UNC-CH and Research Triangle Institute. To accomplish this goal we propose to bring together a group of established investigators, collaborators, and advisors in analytical chemistry. The services provided to the AIDS investigators by the Core will include: specimen procurement and handling of HIV infected and non-infected material; pharmacology consultation and support and support; and the analysis of samples. The analyses will be conducted in a state of the art analytical laboratory that includes high performance liquid chromatography, gas chromatography, capillary electrophoresis nuclear magnetic resonance spectroscopy, and mass spectrometry. The laboratory will be centrally located and have convenient access for the AIDS investigators at UNC-CH. In the absence of the proposed facility important drug assays or other pharmacological studies were either performed by individual investigators, contracted to private firms, or bypassed for lack of funding. The proposed Core should fill all of the analytical and pharmacology needs of AIDS researchers without undue financial burden on their primary grants. In addition, the easy availability of this facility will stimulate new and important AIDS-related drug research. A partial listing of potential projects for the Core, based on current expressed needs of AIDS researchers at UNC-CH and RI, include: 1.) To develop and carry out accurate, sensitive, and specific measurements performed under GLP standards for non-clinical laboratory studies, or drugs used to treat retroviral infection and AIDS-related opportunistic infections. The assays will determine drug concentrations in blood, plasma, cerebrospinal fluid, seminal plasma, urine respiratory fluids, and tissues. 2). To perform pharmacokinetic analysis of drug concentrations in Phase I/II drug development investigators of AIDS-related agents, in drug interaction protocols in specific patient population. 3) To evaluate pharmacodynamic effects of measured rug concentrations. 4) To design and implement original pharmacokinetic/pharmacodynamic research in patients with HIV infections. 5) To provide analytic and pharmacokinetic support of preclinical metabolism studies of novel pro-drugs for treatment of opportunistic infections.
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