EFFICACY OF PROPHYLACTIC AEROSOL AMPHOTERICIN-B LIPID COMPLEX IN A RAT MODEL OF PULMONARY ASPERGILLOSIS

Invasive pulmonary aspergillosis remains an important cause of morbidi ty and mortality among transplant recipients and patients receiving ca ncer chemotherapy, The lipid-associated formulation of amphotericin B (AmB), AmB lipid complex (ABLC), was evaluated for its prophylactic ef ficacy when it was administered as an aerosol in a rat model of pulmon ary aspergillosis. Aerosol ABLC (aero-ABLC), in doses from 0.4 to 1.6 mg/kg of body weight given 2 days before infection, significantly dela yed mortality compared to the mortality of rats given placebo (P < 0.0 01), At day 10 postinfection, 50% of rats in the 0.4-mg/kg group and 7 5% of rats in the 1.6-mg/kg group were alive, while all control animal s had died, In a second trial aero-ABLC was more effective than an equ ivalent dose of aerosol AmB (aero-AmB) in prolonging survival, with 10 0% survival at day 14 postinfection in the ABLC group, compared to 62. 5% survival in the AmB group, Mean concentrations of AmB in lungs were 3.7 times higher at day 1 (P < 0.002) and almost six times higher at day 7 (P < 0.001) after treatment with aero-ABLC than after treatment with a similar dose of aero-AmB. We conclude that aero-ABLC provided h igher and more prolonged levels of the parent compound in the lungs th an aero-AmB and was more effective in delaying mortality from aspergil losis in this model.