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J Pharm Pharmacol. 2000 Jun;52(6):619-27.

Aerosol delivery of amphotericin B desoxycholate (Fungizone) and liposomal amphotericin B (AmBisome): aerosol characteristics and in-vivo amphotericin B deposition in rats.

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Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center Rotterdam, The Netherlands.


In the treatment or prophylaxis of invasive pulmonary aspergillosis, it may be attractive to administer the antifungal agent amphotericin directly to the pulmonary route via aerosol inhalation. In this study, we describe the aerosol characteristics of aerosolized nonliposomal amphotericin B (Fungizone) and liposomal amphotericin B (AmBisome), and the in-vivo aerosol deposition. Aerosols were generated with a Collison nebulizer. Aerosol amphotericin concentrations and mass median diameters were measured. In-vivo pulmonary deposition was evaluated by measuring amphotericin concentrations in lungs of treated rats. Whole body aerosol deposition was determined by measuring radioactivity in tissues of rats after treatment with radiolabelled liposomes. For Fungizone and AmBisome, aerosol amphotericin concentrations were 24.5+/-4.9 and 23.8+/-3.0 microg L(-1), respectively. The values for the median mass diameter were 1.38 and 2.26 microm for Fungizone and 2.43 and 1.97 microm for AmBisome. Amphotericin concentrations in lungs after 60-min nebulization of Fungizone or AmBisome were 24.2+/-6.4 and 21.7+/-2.6 microg g(-1), respectively. After nebulization of radiolabelled liposomes, no radioactivity was retrieved from tissues other than the lungs or the gastrointestinal tract. Nebulization of either Fungizone or AmBisome leads to respirable aerosols and results in a substantial lung tissue concentration of amphotericin and low systemic exposure of amphotericin B. Aerosol administration of either Fungizone or AmBisome may be an attractive approach to prevent or treat pulmonary aspergillosis.

[Indexed for MEDLINE]

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