Efficacy of prophylactic aerosol amphotericin B lipid complex in a rat model of pulmonary aspergillosis Journal Article

Authors: Cicogna, C. E.; White, M. H.; Bernard, E. M.; Ishimura, T.; Sun, M.; Tong, W. P.; Armstrong, D.
Article Title: Efficacy of prophylactic aerosol amphotericin B lipid complex in a rat model of pulmonary aspergillosis
Abstract: 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 duse 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 Arab 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.
Keywords: cancer chemotherapy; controlled study; mortality; placebo; dose response; drug efficacy; nonhuman; animals; animal tissue; animal experiment; animal model; rat; drug tissue level; rats; rats, sprague-dawley; drug half life; drug combinations; aspergillus fumigatus; aspergillosis; lung aspergillosis; drug formulation; drug elimination; organ transplantation; amphotericin b lipid complex; amphotericin b deoxycholate; amphotericin b; phosphatidylcholines; aerosols; antibiotics, antifungal; lung diseases, fungal; male; priority journal; article; phosphatidylglycerols; inhalational drug administration
Journal Title: Antimicrobial Agents and Chemotherapy
Volume: 41
Issue: 2
ISSN: 0066-4804
Publisher: American Society for Microbiology  
Date Published: 1997-02-01
Start Page: 259
End Page: 261
Language: English
PUBMED: 9021176
PROVIDER: scopus
PMCID: PMC163698
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. William Ping-Yiu Tong
    153 Tong
  2. Mary H White
    43 White
  3. Donald Armstrong
    192 Armstrong
  4. Edward M Bernard
    43 Bernard
  5. Ming Sun
    19 Sun