Efficacy of prophylactic aerosol amphotericin B lipid complex in a rat model of pulmonary aspergillosis.
Invasive pulmonary aspergillosis remains an important cause of morbidity and mortality among transplant recipients and patients receiving cancer chemotherapy. The lipid-associated formulation of amphotericin B (AmB), AmB lipid complex (ABLC), was evaluated for its prophylactic efficacy when it was administered as an aerosol in a rat model of pulmonary aspergillosis. Aerosol ABLC (aero-ABLC), in doses from 0.4 to 1.6 mg/kg of body weight given 2 days before infection, significantly delayed mortality compared to the mortality of rats given placebo (P < 0.001). At day 10 postinfection, 50% of rats in the 0.4-mg/kg group and 75% of rats in the 1.6-mg/kg group were alive, while all control animals had died. In a second trial aero-ABLC was more effective than an equivalent dose of aerosol AmB (aero-AmB) in prolonging survival, with 100% 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 higher and more prolonged levels of the parent compound in the lungs than aero-AmB and was more effective in delaying mortality from aspergillosis in this model.
Cicogna
C E
CE
Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
White
M H
MH
Bernard
E M
EM
Ishimura
T
T
Sun
M
M
Tong
W P
WP
Armstrong
D
D
D000336:Aerosols; D000666:Amphotericin B / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001228:Aspergillosis / Q000517:prevention & control*; D001232:Aspergillus fumigatus; D004338:Drug Combinations; D008172:Lung Diseases, Fungal / Q000517:prevention & control*; D008297:Male; D010713:Phosphatidylcholines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010715:Phosphatidylglycerols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000336:Aerosols; D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D000666:Amphotericin B