Deposition of amphotericin B aerosols in pulmonary aspergilloma.
The aim of the present study was to characterize amphotericin B aerosols nebulized by ultrasonic and jet nebulizers and to study their deposition and pharmacokinetics in patients with pulmonary mycetoma. The aerodynamic behaviour and pulmonary deposition of amphotericin B particles were measured using a direct isotopic method based on stable labelling of the drug with 99mTc. Each nebulizer was bench tested for inhaled mass and particle size distribution. Three patients suffering from pulmonary aspergilloma were enrolled for a 4 week clinical study. They received 5 mg of amphotericin B daily delivered by either Fisoneb or DP100 (ultrasonic) or Respirgard II (jet) nebulizers. Deposition of radiolabelled amphotericin B was measured once with each nebulizer using a gamma-camera. In two patients, amphotericin B serum concentration was monitored over a 330 min period after the nebulization had been completed. Inhaled masses of the three nebulizers, assessed as % of labelled drug caught in inspiratory filter in duplicate experiments, were: 5.8 and 3.6% for Respirgard II; 26.5 and 28.3% with Fisoneb; 5.9 and 6.3% for DP100. Mass median aerodynamic diameter (mean +/- SD) results were: 0.28 +/- 0.04 micron with Respirgard II; 4.82 +/- 0.78 microns with Fisoneb; and 2.27 +/- 1.14 microns with DP100. Because of larger particles and significantly greater inhaled mass, Fisoneb delivered more amphotericin B to the central airways, the lung periphery and in the mycetoma lung regions. Amphotericin B serum concentrations correlated with pulmonary deposition and remained below 25 ng.mL-1. No untoward effects were reported by the patients during the 4 week trial.(ABSTRACT TRUNCATED AT 250 WORDS)
D000280:Administration, Inhalation; D000336:Aerosols; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001228:Aspergillosis / Q000188:drug therapy* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008172:Lung Diseases, Fungal / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010215:Papio; D010316:Particle Size; D013667:Technetium
D000336:Aerosols; D000935:Antifungal Agents; D013667:Technetium; D000666:Amphotericin B