Dr. Daniel S. Sitar

Biography

He is a Professor Emeritus in the Department of Pharmacology and Therapeutics at the University of Manitoba, Canada.

Research Interest

The Clinical Pharmacology Section has a long-term interest in issues related to optimization of drug therapy of chronic diseases, especially in elderly patients. My own research focus relates to mechanisms of drug disposition, and their alteration as a result of development and disease processes. One study area includes control mechanisms governing renal excretion of basic drugs. The prototypical model substrate for these studies is amantadine, which was used formerly for influenza A prophylaxis, and currently in the management of Parkinson's disease. Both in vivo studies in animal models and humans and in vitro studies with animal and human kidney tissue are used in order to determine pathologically relevant situations in which renal tubular transport is altered. One focus is on the effects of early diabetes on renal tubular organic cation transport. Another study area encompasses novel conjugation mechanisms in drug metabolism and their potential applications as diagnostic tools. We have demonstrated that amantadine acetylation is mediated solely by spermidine/spermine N1-acetyltransferase. The specificity of this metabolic reaction has implications for the diagnosis of cancer. World-wide patent applications have been filed, and our foundational findings are published. A phase II clinical investigation to determine whether this metabolic reaction can be used for the diagnosis of cancer and/or assessment of the treatment response has been completed and supports our hypothesis. We are now in the planning stage for the phase III study. In addition, our laboratory is involved in collaborative research related to the discovery of new therapeutic targets, and the optimization of drug therapy. Many of these studies are using pharmacokinetic and pharmacodynamic modeling as investigative tools to determine the potential for drug dose modification in relevant patient populations. All of these research projects involve analytical methods by high performance liquid chromatography, gas liquid chromatography, mass spectrometry and radioactive isotope tracer techniques. Data analyses include pharmacokinetic modelling and classic enzyme kinetic approaches. Finally, we continue our studies in clinical toxicology that are directed at evaluating candidate regimens for their potential efficacy in gastrointestinal tract decontamination.