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Pulmonary deposition and disappearance of aerosolised secretory leucocyte protease inhibitor.

作者信息

Stolk J, Camps J, Feitsma H I, Hermans J, Dijkman J H, Pauwels E K

机构信息

Department of Pulmonology, University Hospital, Leiden, The Netherlands.

出版信息

Thorax. 1995 Jun;50(6):645-50. doi: 10.1136/thx.50.6.645.

DOI:10.1136/thx.50.6.645
PMID:7638807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1021265/
Abstract

BACKGROUND

The neutrophil elastase inhibitor, secretory leucocyte protease inhibitor (SLPI), is a potential therapeutic tool in inflammatory lung diseases such as cystic fibrosis and pulmonary emphysema. The distribution and disappearance in the lung of aerosolised recombinant SLPI (rSLPI) was investigated in healthy humans and in patients with cystic fibrosis or alpha 1-antitrypsin-associated emphysema.

METHODS

To distinguish aerosolised rSLPI from endogenous SLPI the recombinant inhibitor was radiolabelled with 99m-technetium (99mTc) pertechnetate. Distribution and disappearance of aerosolised 99mTc-rSLPI in the lungs were studied by gamma radiation imaging.

RESULTS

The deposition of 99mTc-rSLPI in normal volunteers was homogeneous in all lung lobes, while in patients with cystic fibrosis or emphysema only well ventilated areas showed deposition of the aerosol. The disappearance rate of 99mTc-rSLPI was biexponential. The half life of the rapid phase was 0.2-2.8 hours, while that of the slow phase was more than 24 hours.

CONCLUSIONS

Future aerosol therapy with rSLPI will be most beneficial for well ventilated lung tissue that needs protection against neutrophil derived elastase. It may be more difficult to neutralise the burden of elastase in poorly ventilated, highly inflamed areas as are seen in cystic fibrosis.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e0/1021265/4c8f8d15dc3f/thorax00311-0070-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e0/1021265/5d335c2ca9b8/thorax00311-0069-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e0/1021265/852f285c99e6/thorax00311-0070-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e0/1021265/4c8f8d15dc3f/thorax00311-0070-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e0/1021265/5d335c2ca9b8/thorax00311-0069-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e0/1021265/852f285c99e6/thorax00311-0070-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e0/1021265/4c8f8d15dc3f/thorax00311-0070-b.jpg

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Pharmacokinetics of recombinant secretory leukoprotease inhibitor aerosolized to normals and individuals with cystic fibrosis.重组分泌型白细胞蛋白酶抑制剂雾化吸入正常人和囊性纤维化患者后的药代动力学
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