OLSON JA, ADLER-MOORE JP; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. J-1835.
California State Polytechnic University, Pomona, CA
BACKGROUND: Differences in the composition and structure of liposomal amphotericin B (AmBisome) and the amphotericin B-lipid complex (Abelcet) result in marked differences in their pharmacokinetics. The present study was done to determine if the differences in tissue distribution between these two drugs could be correlated with drug levels in the lungs, CFU and survival in an acute murine pulmonary aspergillosis model. METHODS: Immunosuppressed DBA mice (12-15g) were challenged intranasally with 6-8 x 10ex4 Aspergillus fumigatus conidia. Treatment with 15 mg/kg AmBi or Ablt or 5% dextrose was given IV at 2h, 24h, 48h, and 72h post-challenge, and animals (n=7/group, (gp)) were monitored for survival. Log10CFU/g lung (L-CFU/g) and HPLC determinations of drug levels in lungs, plasma, kidneys, liver and spleen were measured 24h after the third treatment. Histopathology of these organs was also done at the same time point. RESULTS: All control mice died by day 5. Survival with 15mg/kg AmBi was greater than for Ablt (86% vs 29%, p=0.039). At 72h post-challenge, the fungal burden in the lung was also markedly lower for AmBi than for Ablt (3.2 L-CFU/g vs 4.5 L-CFU/g, p=0.075). The fungal burden in the control mice was 4.5 L-CFU/g. Ablt had higher drug levels in the lungs than AmBi (36.6 microg/g vs 14.7 microg/g, p=0.002) and in the liver, drug levels were similar (96.6 microg/g for AmBi vs 142.0 microg/g for Ablt, p=0.33). In the spleen, Ablt levels were higher (487.6 microg/g vs 267.7 microg/g, p=0.026), but in the kidneys and serum of the infected mice, AmBi levels were higher (14.5 microg/g vs 10.7 microg/g for kidneys, p=0.03; 3.1 microg/ml vs 0.33 microg/ml for serum, p=0.004). Histopathological analysis of the tissues did not reveal any differences between drug treatments. CONCLUSIONS: The active drug in AmBi appeared to be more bioavailable than Ablt in the lung tissues since less drug in the tissue was needed to produce greater survival and lower CFU/g lung in the infected mice.
Publication Types:
Keywords:
- Abelcet
- AmBisome
- Amphotericin B
- Animals
- Aspergillosis, Allergic Bronchopulmonary
- Aspergillus fumigatus
- Drug Combinations
- Humans
- Lung
- Lung Diseases, Fungal
- Mice
- Mice, Inbred DBA
- Phosphatidylcholines
- Phosphatidylglycerols
- Stem Cells
Other ID:
UI: 102268783
From Meeting Abstracts