Characterization of amphotericin B aerosols for inhalation treatment of pulmonary aspergillosis.
In recent years, the incidence of invasive pulmonary aspergillosis has increased in patients receiving immunosuppressive therapy and/or organ transplantation. For prophylaxis against Aspergillus infections, amphotericin B may be a useful drug when inhaled as aerosol. In this study, the aerosolization of amphotericin B was investigated using eight different medical nebulizers under various operating conditions and with different amphotericin B concentrations in the solution. The output of each nebulizer was characterized by the mass flow of spray (drug) leaving the mouthpiece and by the size distribution of the droplets. An effective prevention of pulmonary aspergillosis via amphotericin B inhalation requires a high pulmonary deposition of the drug within an acceptable time of administration associated with a low deposition in the oropharyngeal region. To evaluate the dosages of drug delivered by various types of nebulizers to different regions of the respiratory tract, a semi-empirical deposition model was applied which is based on experimental aerosol deposition data from over 20 normal adults. The main results of the study are: Solutions with amphotericin B concentrations up to 10 mg/ml can be converted into sprays by means of medical nebulizers without any problems. For most nebulizers, the slight foaming of the amphotericin B solution has no effect on the production of the aerosol. To optimize amphotericin B treatment of the lungs via inhalation, sprays with mass flows above 100 mg/min and with mass median aerodynamic diameters (MMAD) below 3 microns should be slowly inhaled by the subject. Applying these criteria to the nebulizers investigated, three out of eight devices have proved suitable for amphotericin B treatment via inhalation.
Roth
C
C
GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Inhalationsbiologie, Oberschleissheim, Germany.
Gebhart
J
J
Just-Nübling
G
G
von Eisenhart-Rothe
B
B
Beinhauer-Reeb
I
I
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols / Q000032:analysis; D000666:Amphotericin B / Q000008:administration & dosage* / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D008172:Lung Diseases, Fungal / Q000188:drug therapy*; D008297:Male; D008954:Models, Biological; D009330:Nebulizers and Vaporizers
D000336:Aerosols; D000666:Amphotericin B