Clinically achievable plasma deferoxamine concentrations are therapeutic in a rat model of Pneumocystis carinii pneumonia.
The iron-chelating drug deferoxamine (DFO) has been shown to be active in animal models of Pneumocystis carinii pneumonia (PCP), with effective daily intraperitoneal bolus dosages being 400 and 1,000 mg of DFO mesylate kg of body weight-1 in mouse and rat models, respectively. Continuous infusion produced a moderately improved response in a rat model. The data reported here demonstrate that the response achieved by continuous infusion of 195 and 335 mg of DFO mesylate kg-1 day-1 in the rat model is associated with mean concentrations in plasma of 1.3 and 2.5 micrograms of DFO ml-1 and mean concentrations in lung tissue of 4.9 and 6.0 micrograms of DFO g of lung tissue-1, respectively. Since current clinical use of DFO mesylate for the treatment of iron overload produces higher concentrations in the plasma of patients, DFO may prove to be a useful anti-PCP treatment. The 2.4- to 3.8-fold higher DFO concentration observed in lung tissue compared with that observed in plasma may be important in the response of PCP to DFO.
Merali
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S
Department of Medical and Molecular Parasitology, New York University School of Medicine, New York 10016, USA.
Chin
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Del Angel
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Grady
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Armstrong
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Clarkson
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D000818:Animals; D000935:Antifungal Agents / Q000097:blood* / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003676:Deferoxamine / Q000097:blood* / Q000627:therapeutic use*; D008168:Lung / Q000382:microbiology; D051379:Mice; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000382:microbiology; D051381:Rats
D000935:Antifungal Agents; D003676:Deferoxamine