Selective Delivery of Pentamidine to the Lung by Aerosol

Abstract
In 8 patients with diffuse infiltrates on chest radiograph undergoing fiberoptic bronchoscopy for suspected Pneumocystis carinii pneumonia, bronchoalveolar lavage sediment and supernatant concentrations of pentamidine were compared 18 to 24 h after administration of 4 mg/kg intravenous (n = 3) and aerosolized (n = 5) pentamidine isethionate. Aerosol was inhaled for 35 to 40 min with 300 mg pentamidine isethionate in a jet nebulizer, baffled to decrease the particle size to 1.42 .mu.m .+-. 1.88 (mass median aerodynamic diameter .+-. geometric standard deviation). Bronchoalveolar pentamidine concentrations were: in sediment, 9.34 .+-. 1.74 postintravenous versus 705 .+-. 242 ng/ml postaerosol (mean .+-. SEM, p < 0.05); supernatant, 2.64 .+-. 0.73 postintravenous versus 23.2 .+-. 7.75 ng/ml postaerosol (mean .+-. SEM, p < 0.05). Serum pentamidine levels were low or undetectable after aerosolization. Aerosol administration delivers significantly higher concentrations of pentamidine to the air spaces than does intravenous delivery in patients with diffuse alveolar infiltrates.