Document Detail


Insulin Lung Deposition and Clearance Following Technosphere(®) Insulin Inhalation Powder Administration.
MedLine Citation:
PMID:  21491144     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: To determine distribution and deposition of Technosphere(®) Insulin (TI) inhalation powder and the rate of clearance of fumaryl diketopiperazine (FDKP; major component of Technosphere particles) and insulin from the lungs. METHODS: Deposition and distribution of (99m)pertechnetate adsorbed onto TI immediately after administration using the MedTone® inhaler was quantified by gamma-scintigraphy. Clearance from the lungs was studied in a second experiment by serial bronchoalveolar lavage (BAL) after administration of TI inhalation powder and assay of the recovered fluid for FDKP and insulin. RESULTS: Following inhalation, ~60% of radioactivity (adsorbed on TI) emitted from the inhaler was delivered to the lungs; the remainder of the emitted dose was swallowed. Clearance from the lung epithelial lining fluid (ELF) of FDKP and insulin have a half-life of ~1 hour. CONCLUSION: TI inhalation powder administered via the MedTone inhaler was uniformly distributed throughout the lungs; ~40% of the initial cartridge load reached the lungs. Insulin and FDKP are quickly cleared from the lungs, mainly by absorption into the systemic circulation. The terminal clearance half-life from the lung ELF, estimated from sequential BAL fluid measurements for both components, was ~1 hour. Since there is an overnight washout period, the potential for accumulation on chronic administration is minimal.
Authors:
James P Cassidy; Nikhil Amin; Mark Marino; Mark Gotfried; Thomas Meyer; Knut Sommerer; Robert A Baughman
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-14
Journal Detail:
Title:  Pharmaceutical research     Volume:  -     ISSN:  1573-904X     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
MannKind Corporation, Valencia, California, USA, jcassidy@mannkindcorp.com.
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