Pharmacokinetics of recombinant secretory leukoprotease inhibitor aerosolized to normals and individuals with cystic fibrosis. Academic Article Article uri icon

Overview

MeSH

  • Aerosols
  • Analysis of Variance
  • Bronchi
  • Bronchoalveolar Lavage Fluid
  • Drug Evaluation
  • Epithelium
  • Female
  • Humans
  • Male
  • Proteinase Inhibitory Proteins, Secretory
  • Recombinant Proteins
  • Secretory Leukocyte Peptidase Inhibitor

MeSH Major

  • Cystic Fibrosis
  • Proteins
  • Serine Proteinase Inhibitors

abstract

  • Recombinant secretory leukoprotease inhibitor (rSLPI), a recombinant form of a natural airway inhibitor of neutrophil elastase (NE), is a potential therapeutic agent for cystic fibrosis (CF), a condition characterized by airway derangement mediated in part by the large burden of NE on the CF respiratory epithelial surface. After in vitro studies that demonstrated that aerosolized rSLPI retains its form and function, rSLPI was administered via aerosol to normal individuals and individuals with CF to determine the pharmacokinetics of in vivo rSLPI augmentation of the anti-NE defenses of the respiratory epithelial surface. After rSLPI aerosolization to normal individuals (100 mg single dose or 100 mg twice daily for 1 wk) there was a marked increase in SLPI levels and anti-NE capacity in airway epithelial lining fluid (ELF) at 1 h, diminishing gradually over 4 to 12 h. Interestingly, the ELF SLPI levels and anti-NE capacity achieved 12 h after 1 wk of rSLPI aerosols were no different than those 12 h after a single dose of rSLPI, suggesting that rSLPI does not accumulate on the respiratory epithelial surface after aerosolization. The ability of rSLPI to suppress NE in vivo was evaluated by aerosolization of rSLPI to individuals with CF, first as an escalating dose to assess safety, and then at doses of 100 mg twice daily for 1 wk or 50 mg twice daily for 2 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

publication date

  • October 1993

has subject area

  • Aerosols
  • Analysis of Variance
  • Bronchi
  • Bronchoalveolar Lavage Fluid
  • Cystic Fibrosis
  • Drug Evaluation
  • Epithelium
  • Female
  • Humans
  • Male
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • Recombinant Proteins
  • Secretory Leukocyte Peptidase Inhibitor
  • Serine Proteinase Inhibitors

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1164/ajrccm/148.4_Pt_1.1056

PubMed ID

  • 8105734

Additional Document Info

start page

  • 1056

end page

  • 1060

volume

  • 148

number

  • 4 Pt 1