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 effect ive 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 m odel. 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 mu g of DFO ml(-1) and mean concentrations in lung tissue o f 4.9 and 6.0 mu g of DFO g of lung tissue(-1), respectively. Since cu rrent clinical use of DFO mesylate for the treatment of iron overload produces higher concentrations in the plasma of patients, DFO may prov e to be a useful anti-PCP treatment. The 2.4- to 3.8-fold higher DFO c oncentration observed in lung tissue compared with that observed in pl asma may be important in the response of PCP to DFO.