The nebulization of
amphotericin B desoxycholate (AMB-DOC),
liposomal amphotericin B (
L-AMB),
amphotericin B lipid complex (ABLC) and
amphotericin B colloidal dispersion (ABCD) has been investigated. Particle sizes of generated
aerosol droplets were measured. Pulmonary
amphotericin B deposition and
amphotericin B concentration in blood directly after nebulization and at six weeks after nebulization was measured in healthy rats. The efficacy of nebulized
amphotericin B formulations was evaluated in persistently granulocytopenic rats with
invasive pulmonary aspergillosis. Treatment was given either after or before fungal inoculation. The endpoint was survival of animals.
Aerosol particle sizes, expressed as the values for the mass median diameter were 1.38, 2.43, 0.90 and 2.29 microm for AMB-DOC,
L-AMB, ABLC and ABCD, respectively.
Amphotericin B concentrations in the lungs directly after nebulization exceeded the minimum inhibitory concentration of Aspergillus fumigatus and
amphotericin B was still detected in lungs of rats at six weeks after nebulization. Treatment, started at 16 h after fungal inoculation, resulted in a significantly prolonged survival as compared with
sham-treated rats for all four formulations. Prophylactic treatment at one week before fungal inoculation resulted in a significantly prolonged survival for all four formulations.
Aerosol treatment given at two weeks before inoculation was effective only for AMB-DOC and
L-AMB, whereas treatment given at six weeks resulted in a significantly prolonged survival for
L-AMB only. All commercially available
amphotericin B preparations could be nebulized efficiently and may be of value in the prophylactic treatment of
invasive pulmonary aspergillosis.