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 Tc-99m, 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(R) or DP100(R) (ultrasonic) or Respirgard II(R) (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(R); 26.5 and 28.3% with Fisoneb(R); 5.9 and 6.3% for DP100(R). Mass median aerodynamic diameter (mean +/- SD) results were: 0.28 +/- 0.04 mu m with Respirgard II(R); 4.82 +/- 0.78 mu m with Fisoneb(R); and 2.27 +/- 1.14 mu m with DP100(R). Because of larger particles and significantly greater inhaled mass, Fisoneb(R) 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.