Direct isotopic assessment of aerosolized pentamidine deposition: influence of nebuliser

The aim of the present study was to compare the efficiency of pulmonary deposition of pentamidine using the Respirgard II jet nebuliser or the Fison ultrasonic nebuliser with 99m technetium (99m Tc) labelled pentamidine in the current conditions of recommended treatment. The study was designed in three stages, to verify particle size distribution, to validate the isotope labelling, and to compare pulmonary deposition of pentamidine isethionate with the two nebulisers.

Count median aerodynamic diameter and mass median aerodynamic diameter were measured using the velocimetry technique and aerosol dispersion was calculated according to the standard deviation defined by the ratio of diameters between 84.3% and 50% of the total distribution. Stability of labelling was checked both in vitro, by radiochromatography, and in vivo, by the absence of free technetium thyroid fixation after intravenous injection of the preparation to a rat and inhalation by baboons. The direct isotopic technique was used to compare pulmonary deposition of 300 mg aerosolized 99m Tc labelled pentamidine isothionate with the two nebulisers in four HIV patients treated with primary prophylaxis.

Count median aerodynamic diameter and mass median aerodynamic diameter (MMAD) were higher with Fisoneb than with Respirgard II. Nevertheless Fisoneb MMAD remained in the optimal range for peripheral deposition. In one patient, pentamidine lung burden was higher using the Respirgard II (13% of dose originally in nebuliser) when compared with the Fisoneb (10.2% of dose originally in nebuliser). A better result was obtained in the 3 other patients with Fisoneb (mean = 14.3%) compared with Respirgard II (mean = 3.8%). In all 4 patients gastric contamination was higher with Fisoneb (mean = 5.2%) as compared with Respirgard II (mean = 2.6%). Cough and bronchospasm were not observed with either device.

This study showed that Fisoneb, a practical and cheap nebuliser which has proved to be effective in clinical studies when used for pentamidine nebulisation, leads to correct particle size distribution and pulmonary deposition of the drug. We believe that such studies to evaluate aerosol characteristics should be recommended for any kind of nebuliser.