Our long-term objective is to proved a pharmacologic basis for the selection of potential anti-AIDS agents designed and synthesized by our Group for further studies leading ultimately to their clinical trial. Specifically, we plan first to study the physical, physicochemical, and pharmaceutical properties and to develop analytical methodologies for the quantitation of these agents in biological specimens. Based on these, we shall study the absorption, bioavailability, transport distribution, protein-binding, excretion and metabolism of these agents. From plasma drug concentration versus time graphs after drug administration by different dose, schedule, and routes, we shall compute pharmacokinetic parameters such as plasma peak drug concentration, elimination half-life, various apparent volumes of distribution, and rates of total clearance. Attempts will be made to isolate and identify drug metabolites so that their anti-AIDS virus activities may be evaluated. Included in our studies are pyrophosphate analogues, 3'-substituted deoxythymidine triphosphates and certain naturally occurring tannins. Naturally, drugs with the most desirable pharmacologic properties will be the logical candidates for extensive development. Moreover, knowledge gained from our research promises to aid in the design of the best protocol for the clinical trial of these new agents.
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