The Division of Acquired Immune Deficiency Syndrome (AIDS) and the Microbiology and Infectious Disease Program of the National Institute of Allergy and Infectious Diseases are actively engaged in programs to: carry out basic investigations of the infectious disease process, and discover novel therapeutic approaches to treat these conditions via the National Cooperative Drug Discovery Group mechanism and screening programs. These therapies are directed at a wide variety of infectious diseases including those produced by HIV, cytomegalovirus, Herpes simplex, Pneumocystis pneumonia, Candida albicans, Mycobacterium avium complex, etc. Some but not all of the NIAID funded drug discovery mechanisms have the capability and capacity to carry out the required studies to convert chemicals exhibiting activity in a predictive in vitro test system or animal model into a pharmaceutical dosage form manufactured on sufficient scale to permit phase I and II clinical evaluation of the substance. This initiative provides analytical chemistry/quality control capability to verify the identity and assess the purity of the chemicals prior to evaluation in: in vivo animal models, toxicology studies, pharmaceutical dosage forms, and clinical trials. In addition, the contractor will evaluate the solubility and stability of these agent and recommend procedures for the appropriate handling of these compounds during evaluation in vivo models of efficacy and toxicity. Determinations of partition coefficients, pKa's, and Ph versus stability profiles, will be used to obtain preliminary information on a new compound that may predict for biologic behavior. The contractor will also assay the final dosage form and assess its stability over time. Methodology to estimate the drug in blood and urine also will be developed.
