Aerosol-Based Efficient Delivery of Clarithromycin, a Macrolide Antimicrobial Agent, to Lung Epithelial Lining Fluid and Alveolar Macrophages for Treatment of Respiratory Infections

2012 ◽  
Vol 25 (2) ◽  
pp. 110-115 ◽  
Author(s):  
Kohei Togami ◽  
Sumio Chono ◽  
Kazuhiro Morimoto
Metabolomics ◽  
2018 ◽  
Vol 14 (10) ◽  
Author(s):  
Joost Brandsma ◽  
◽  
Victoria M. Goss ◽  
Xian Yang ◽  
Per S. Bakke ◽  
...  

1993 ◽  
Vol 75 (2) ◽  
pp. 825-832 ◽  
Author(s):  
A. Gillissen ◽  
P. Birrer ◽  
N. G. McElvaney ◽  
R. Buhl ◽  
C. Vogelmeier ◽  
...  

Secretory leukoprotease inhibitor (SLPI), a 12-kDa serine antiprotease, serves as the major inhibitor of neutrophil elastase (NE) on the epithelial surface of the upper airways. As a control for studies to evaluate the aerosol administration of recombinant SLPI (rSLPI) to augment the anti-NE defenses of the lung, the status of antioxidants in respiratory epithelial lining fluid (ELF) was evaluated. Unexpectedly, aerosol administration of rSLPI caused an elevation in ELF glutathione, a major component of the epithelial antioxidant screen; i.e., rSLPI may provide not only augmentation of anti-NE defenses but also antioxidant defenses. To evaluate this concept, rSLPI (100 mg) was aerosolized to sheep, and SLPI, glutathione, anti-NE capacity, and anti-H2O2 capacity were evaluated in respiratory ELF over a 30-h period. As expected, aerosolization of rSLPI increased ELF SLPI levels and anti-NE capacity. Strikingly, postaerosol levels of glutathione in ELF were also increased (5-fold 24 h after aerosol), with a concomitant increase in ELF anti-H2O2 capacity; i.e., the rSLPI augmented the antioxidant screen of ELF. This suggests that rSLPI may be particularly well suited for therapy in lung diseases characterized by excess of both serine proteases and oxidants on the respiratory epithelial surface.


2005 ◽  
Vol 66 (10) ◽  
pp. 1770-1774 ◽  
Author(s):  
Harry W. Boothe ◽  
Sarah A. Jones ◽  
W. Scott Wilkie ◽  
Albert Boeckh ◽  
Kristol K. Stenstrom ◽  
...  

1997 ◽  
Vol 41 (6) ◽  
pp. 1399-1402 ◽  
Author(s):  
K A Rodvold ◽  
M H Gotfried ◽  
L H Danziger ◽  
R J Servi

The steady-state concentrations of clarithromycin and azithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained in intrapulmonary samples during bronchoscopy and bronchoalveolar lavage from 40 healthy, nonsmoking adult volunteers. Mean plasma clarithromycin, 14-(R)-hydroxyclarithromycin, and azithromycin concentrations were similar to those previously reported. Clarithromycin was extensively concentrated in ELF (range of mean +/- standard deviation concentrations, 34.4 +/- 29.3 microg/ml at 4 h to 4.6 +/- 3.7 microg/ml at 24 h) and AM (480 +/- 533 microg/ml at 4 h to 99 +/- 50 microg/ml at 24 h). The concentrations of azithromycin in ELF were 1.01 +/- 0.45 microg/ml at 4 h to 1.22 +/- 0.59 microg/ml at 24 h, and those in AM were 42.7 +/- 28.7 microg/ml at 4 h to 41.7 +/- 12.1 microg/ml at 24 h. The concentrations of 14-(R)-hydroxyclarithromycin in the AM ranged from 89.3 +/- 52.8 microg/ml at 4 h to 31.3 +/- 17.7 microg/ml at 24 h. During the period of 24 h after drug administration, azithromycin and clarithromycin achieved mean concentrations in ELF and AM higher than the concomitant concentrations in plasma.


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