Am. J. Respir. Crit. Care Med., Vol 155, No. 2, 02 1997, 536-541.
The intrapulmonary half-life and safety of aerosolized alpha1-protease inhibitor in normal volunteers
C Vogelmeier, I Kirlath, S Warrington, N Banik, E Ulbrich and RM Du Bois
Pneumologische Abteilung, Medizinische Klinik und Poliklinik I, Klinikum Grosshadern, University of Munich, Germany.
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.
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Copyright © 1997 American Thoracic Society
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