EFFECTS OF AEROSOLIZED SYNTHETIC SURFACTANT, ATOVAQUONE, AND THE COMBINATION OF THESE ON MURINE PNEUMOCYSTIS-CARINII PNEUMONIA

An immunosuppressed rat model was used to determine the pharmacokineti cs of aerosolized atovaquone (administered with and without a syntheti c surfactant) and to evaluate the efficacy of inhaled atovaquone in th e prevention and treatment of Pneumocystis carinii pneumonia (PCP). Af ter a single dose by aerosol, mean peak concentrations of atovaquone a veraged 52 mu g/mL in plasma and 31 mu g/g in lungs of rats infected w ith P. carinii. When atovaquone was combined with surfactant, mean pea k concentrations of 93 mu g/mL in plasma and 51 mu g/g in lung were ac hieved. Aerosolized synthetic surfactant alone significantly increased survival of rats with PCP and, when combined with atovaquone, increas ed plasma and lung concentrations of the drug and eradication of the o rganism.