Delivered dose and regional distribution of aerosolized pentamidine using different delivery systems

Aerosolized pentamidine has gained acceptance as a form of treatment for the prevention of Pneumocystis carinii pneumonia. However, different studies have used different delivery systems, making comparison of results difficult. This study was designed to determine the dose to the lung, regional distribution, extrapulmonary deposition, and side effects using four different delivery systems: the Respirgard II, the Aero Tech II, the Portasonic, and the Fisoneb. Ten homosexual subjects who were infected with HIV virus were studied. Particle size, as determined by cascade impaction, varied among nebulizers. Mass median aerodynamic diameter was 0.90 mu for the Respirgard II, 1.30 mu for the Aero Tech II, 1.40 mu for the Portasonic, and 3.90 mu for the Fisoneb. Subjects inhaled a solution containing 60 mg pentamidine in 3 ml of sterile water, and 1 ml of 99mTc bound to human serum albumin for each nebulizer system. Regional distribution was determined by comparing each deposition scan obtained by a posteriorly positioned gamma camera to the subjects' equilibrium xeon scan. The deposition scan was used to quantitate lung dose and extrapulmonary deposition. Marked differences were seen among delivery systems. Dose to the lung varied fivefold. The deposition in the lung, expressed as a percentage of the amount placed in the nebulizer, was 5.3 percent in the Respirgard II, 15.7 percent in the Aero Tech II, 17.30 percent in the Portasonic, and 26.4 percent in the Fisoneb (p less than 0.0001 by ANOVA). Wide differences in extrapulmonary deposition and side effects were noted among nebulizers (Fisoneb greater than Portasonic, Aero Tech II greater than Respirgard II). Regional distribution in the lung as measured by the AI, also showed differences, with the Respirgard having the most homogeneous distribution of aerosol (Respirgard greater than Portasonic, Aero Tech greater than Fisoneb). Regional distribution and extrapulmonary deposition varied in a manner consistent with the particle size of the nebulizers. These data should provide a framework for the comparison and design of future clinical studies using these delivery systems.