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 neburilation 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 μm with Respirgard II®; 4.82±0.78 μm with Fisoneb®; and 2.27±1.14 μm 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. This study demonstrates that amphotericin B suspension can be accurately radiolabelled, is effectively nebulized by a variety of nebulizers, and is well-tolerated by human subjects.