title: The intrapulmonary half-life and safety of aerosolized alpha1-protease inhibitor in normal volunteers.
abstract: Aerosol delivery of alpha1-protease-inhibitor (alpha1-PI) has the potential for reducing the amount of alpha1-PI needed to treat persons who are severely alpha1-PI-deficient, thereby decreasing the high cost of treatment and making alpha1-PI available to treat many alpha1-PI-deficient persons who do not now have access to that product. Aerosolized alpha1-PI may also be useful in cystic fibrosis. The goal of our study was to evaluate the duration of action of aerosolized alpha1-PI and possible side effects in normal volunteers. Twenty-nine volunteers underwent bronchoalveolar lavage (BAL) and 3 to 7 d later inhaled 200 mg of alpha1-PI. Subjects were subsequently assigned to one of five groups; a second BAL was performed 0.5, 6, 12, 24, or 36 h after the aerosol, respectively. The BAL fluid samples were analyzed for alpha1-PI concentrations, anti-neutrophil elastase (NE) activity, cell count and differential, alpha1-PI-NE complex level, and uptake of alpha1-PI by alveolar macrophages. Overall we observed no substantial side effects. The one-time alpha1-PI aerosol induced a significant increase of alpha1-PI concentrations as well as anti-NE activity. Even in the BAL fluid samples obtained 36 h after aerosol administration alpha1-PI concentrations and anti-NE activity were about double baseline values. The half-time in the lungs for alpha1-PI concentrations and anti-NE activity were about double baseline values. The half-time in the lungs for alpha1-PI was 69.2 h and for anti-NE activity was 53.2 h, respectively. We conclude from our data in normal volunteers that inhalation of aerosolized alpha1-PI may be a safe, effective, and conveniently administered therapy for persons with severe alpha1-PI deficiency; this mode of administration warrants further study.
authors.affiliation: Pneumologische Abteilung, Medizinische Klinik und Poliklinik I, Klinikum Grosshadern, University of Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Vogelmeier
authors.forename: I
authors.initials: I
authors.lastname: Kirlath
authors.forename: S
authors.initials: S
authors.lastname: Warrington
authors.forename: N
authors.initials: N
authors.lastname: Banik
authors.forename: E
authors.initials: E
authors.lastname: Ulbrich
authors.forename: R M
authors.initials: RM
authors.lastname: Du Bois
mesh_terms: D000328:Adult; D000336:Aerosols; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism*; D012129:Respiratory Function Tests; D012449:Safety; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019896:alpha 1-Antitrypsin Deficiency
chemical_list: D000336:Aerosols; D000515:alpha 1-Antitrypsin