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Deposition of amphotericin B aerosols in pulmonary aspergilloma
1Service de Pneumologie, Unité d'Evaluation Clinique, CHU Bretonneau, Tours, France.
Abstract:
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)
Insights
This study compared ultrasonic and jet nebulizers for delivering amphotericin B for pulmonary mycetoma. The Fisoneb ultrasonic nebulizer showed greater lung deposition due to larger particles and higher inhaled mass.
Area of Science:
- Pulmonary Medicine
- Pharmacokinetics
- Medical Devices
Background:
- Pulmonary mycetoma requires effective antifungal drug delivery.
- Amphotericin B is a key antifungal, but its pulmonary delivery needs optimization.
- Nebulizer technology impacts drug deposition and efficacy.
Purpose of the Study:
- To characterize amphotericin B aerosols from ultrasonic and jet nebulizers.
- To evaluate pulmonary deposition and pharmacokinetics of nebulized amphotericin B.
- To compare the performance of Fisoneb, DP100 (ultrasonic), and Respirgard II (jet) nebulizers.
Main Methods:
- Bench testing of nebulizers for inhaled mass and particle size distribution using stable isotope labeling (99mTc).
- Clinical study involving three patients with pulmonary aspergilloma receiving daily amphotericin B.
- Gamma-camera imaging for pulmonary deposition and serum concentration monitoring.
Main Results:
- The Fisoneb nebulizer produced larger particles (4.82 ± 0.78 μm) and higher inhaled mass (26.5–28.3%) compared to DP100 (2.27 ± 1.14 μm; 5.9–6.3%) and Respirgard II (0.28 ± 0.04 μm; 3.6–5.8%).
- Fisoneb demonstrated significantly greater amphotericin B delivery to central airways, lung periphery, and mycetoma regions.
- Amphotericin B serum concentrations remained low (<25 ng/mL) and correlated with pulmonary deposition.
Conclusions:
- Nebulizer choice significantly affects amphotericin B pulmonary deposition.
- The Fisoneb ultrasonic nebulizer offers superior delivery for pulmonary mycetoma treatment due to particle size and inhaled mass.
- Nebulized amphotericin B showed favorable pharmacokinetics with minimal systemic absorption.