NEW METHODS FOR DETERMINATION OF PENTAMIDINE

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The aim of this project is to develop a chemical reagent that can be used to directly measure pentamidine in blood or other fluids from AMS patients undergoing therapy for Pneumocystis carinii pneumonia. This reagent is a synthetic organic molecule containing a dye that would fluoresce upon binding pentamidine. The reagent could be mixed with blood or lung lavage samples enabling determination of pentamidine concentration by spectrofluorometric assay. Alternately, the synthetic pentamidine receptor could be used to construct a fiber optic chemical sensor for measuring pentamidine reversibly in a flow system or in vivo. Pentamidine isethionate is currently the drug of choice for treatment of Pneumocystis carinii pneumonia, the leading killer of AIDS patients. It is also administered by inhalation to prevent recurrence of this AIDS-related disease. Pentamidine is toxic and its pharmacokinetics and optimum administration protocols have yet to be fully determined. Current methods for pentamidine measurement involve laboratory manipulation of blood extracts, requiring considerable time. The proposed analysis method would be fast and would involve minimum risk of HIV infection for personnel. The proposed project involves synthesis of several derivatives of a compound that has already been found to bind pentamidine in extraction and ion-selective electrode experiments. The fluorescent dye is to be introduced as part of the framework of this molecule. Variable functional groups will then be used to achieve the correct physical properties, enabling the synthetic receptor to bind pentamidine strongly, selectively and with a fluorescent response.