The purpose of this Core will be to provide pharmacology services, to oversee biological sample collection and analysis, and to manage the data generated by the three projects. Specific functions will include implementation of the randomization procedure, preparation of study drugs and placebos, carrying out measurements of antimalarial drug concentrations in plasma, cultivation of parasites and compilation of the clinical data. Serial plasma concentrations of artesunate, desferrioxamine B and quinine will be determined before and after initial dosing, and steady state concentrations will be monitored. Careful attention will be given to the collection, distribution and processing of biologic samples, including (i) blood, urine and cerebrospinal fluid for clinical specimens for purposes in Project 1, (ii) brain and other tissues obtained at autopsy for Project 2, (iii) malaria parasite specimens for analysis in Project 3, (iv) plasma samples for determining drug levels in and (v) blood parasites will be particularly useful for the biochemical studies proposed in Project 3. The clinical data generate by Project 1 will be collected, tabulated and compiled in data files for correlation with the information produced by the other Projects and Cores. The specific objectives of this Core are: 1. To provide pharmacology services for Project 1 and to determine plasma levels of artesunate, desferrioxamine B and quinine in study patients. 2. To oversee collection, distribution and storage of biologic samples, including the isolation and preparation of stabilitates of parasites from all patients on admission and whenever recrudescence occur. 3. To provide general support services including the complication and monitoring of clinical and basic science data. The services provided by this Core will be critical to the success of Projects 1,2 and 3. The efforts of this Core will facilitate the overall goal of defining the role of iron in the antimalarial mechanisms of artesunate and desferrioxamine B and in the pathophysiology of cerebral malaria.
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