Production and administration to dogs of aerosols of alpha-1-proteinase inhibitor.
The feasibility of aerosol administration of alpha-1-proteinase inhibitor (human) (A1PI) was assessed. Of three different methods of aerosolizing A1PI that were evaluated, an ultrasonic nebulizer was found to be best suited to the present purpose, producing particles of a size that allowed them to reach the distal air spaces of the lung and that retained specific A1PI anti-elastase activity. Administration of 20 mg/kg of A1PI and 150 microCi of 131iodine-A1PI to three dogs was accomplished without complications. Gamma camera scans documented a relatively homogenous distribution throughout the lungs. Bronchial lavage fluid that was recovered from the lungs of the dogs six hours after administration contained large amounts of human A1PI and showed a proportional elevation of anti-elastase activity. There was no evidence of acute toxicity.
Smith
R M
RM
Department of Medicine, University of California, San Diego.
Spragg
R G
RG
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001798:Blood Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D004285:Dogs; D007457:Iodine Radioisotopes; D008168:Lung / Q000378:metabolism; D009330:Nebulizers and Vaporizers; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012588:Scintillation Counting; D000515:alpha 1-Antitrypsin
D000336:Aerosols; D001798:Blood Proteins; D007457:Iodine Radioisotopes; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin