THE INTRAPULMONARY HALF-LIFE AND SAFETY OF AEROSOLIZED ALPHA-1-PROTEASE INHIBITOR IN NORMAL VOLUNTEERS

Aerosol delivery of alpha 1-protease-inhibitor (alpha 1-PI) has the po tential for reducing the amount of alpha 1-PI needed to treat persons who are severely alpha 1-PI-deficient, thereby decreasing the high cos t of treatment and making alpha 1-PI available to treat many alpha 1-P I-deficient persons who do not now have access to that product. Aeroso lized alpha 1-PI may also be useful in cystic fibrosis. The goal of ou r study was to evaluate the duration of action of aerosolized alpha 1- PI and possible side effects in normal volunteers. Twenty-nine volunte ers underwent bronchoalveolar lavage (BAL) and 3 to 7 d later inhaled 200 mg of alpha 1-PI. Subjects were subsequently assigned to one of fi ve groups; a second BAL was performed 0.5, 6, 12, 24, or 36 h after th e aerosol, respectively. The BAL fluid samples were analyzed for alpha 1-PI concentrations, anti-neutrophil elastase (NE) activity, cell cou nt and differential, alpha 1-PI-NE complex level, and uptake of alpha 1-PI by alveolar macrophages. Overall we observed no substantial side effects. The one-time alpha 1-PI aerosol induced a significant increas e of alpha 1-PI concentrations as well as anti-NE activity. Even in th e BAL fluid samples obtained 36 h after aerosol administration alpha 1 -PI concentrations and anti-NE activity were about double baseline val ues. The half-time in the lungs for alpha 1-PI concentrations and anti -NE activity were about double baseline values. The half-time in the l ungs for alpha 1-PI was 69.2 h and for anti-NE activity was 53.2 h, re spectively. We conclude from our data in normal volunteers that inhala tion of aerosolized alpha 1-PI may be a safe, effective, and convenien tly administered therapy for persons with severe alpha 1-PI deficiency ; this mode of administration warrants further study.