Aerosolization Potential of Amphotericin B Lipid Complex

A. WONG-BERINGER 1, M. LAMBROS 2, D. JOHNSON 3

Author address: 

1 Univ. of Southern California, Los Angeles, CA, 2 Western Univ., Pomona, CA, 3 Univ. of Oklahoma, OK.

Abstract: 

Background: Aerosolized amphotericin B therapy has been utilized as prophylaxis in patients at high risk for developing invasive pulmonary aspergillosis. Thus far, the physicochemical (PC) properties of the aerosol have not been well characterized, which may affect airway tolerability and the efficiency of the nebulization system. We evaluated suspensions of amphotericin B lipid complex (ABLC) as aerosols and the efficiency of different nebulization systems. Methods: PC measurements of suspensions of amphotericin B lipid complexes (Abelcet) (5 and 10mg/ml) were performed: osmolality, pH, viscosity, and surface tension. Each solution was nebulized via 3 compressor-nebulizer systems to assess nebulizer efficiency (drug output and respirable fraction). Andersen Cascade impactor was used to determine aerosol particle size and distribution. The respirable fraction (RF) is defined as the % of aerosolized particles with an aerodynamic diameter of 1-3.5 μm. HPLC was used to quantify drug deposited on the stages of the cascade impactor. Results: The osmolality, pH and Cl- content of both concentrations of amphotericin B-lipid complex suspensions were within the desirable values, pH 7.4, osmolality (150-550 mOsm/kg) and Cl- content (31-300mM). Drug output and RF differ by nebulizing systems and concentrations of aerosol solution. Foaming was observed. Conclusions: Study results suggest that Proneb-Pari LC Star is most efficient in delivering drug in RF optimal for lung deposition; however nebulization time will need to be significantly prolonged beyond 10 minutes in order to deliver a dose of 50mg ABLC for all nebulizers tested. [Table1]
2004

abstract No: 

M-1060-200

Full conference title: 

44th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 44th