caa a22 4500 445311932 CHVBK 20180317142633.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s11095-011-0443-4 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0443-4 Insulin Lung Deposition and Clearance Following Technosphere® Insulin Inhalation Powder Administration [Elektronische Daten] [James Cassidy, Nikhil Amin, Mark Marino, Mark Gotfried, Thomas Meyer, Knut Sommerer, Robert Baughman] ABSTRACT: 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 99mpertechnetate 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 ~1hour. Since there is an overnight washout period, the potential for accumulation on chronic administration is minimal. Springer Science+Business Media, LLC, 2011 Afrezza® nationallicence fumaryl diketopiperazine nationallicence inhalation powder nationallicence insulin clearance nationallicence insulin lung disposition nationallicence Technosphere Insulin inhalation powder nationallicence Tc : 99mTechnetium nationallicence AUC0-t : area under the insulin concentration-time curve from 0 to time t nationallicence BAL : bronchoalveolar lavage nationallicence ELF : epithelial lining fluid of the lungs nationallicence FDKP : fumaryl diketopiperazine nationallicence FEV1 : forced expiratory volume in 1s nationallicence IVC : inspiratory vital capacity nationallicence MEF25%FVC : mid-expiratory flow at 25% of forced vital capacity nationallicence MEF50%FVC : mid-expiratory flow at 50% of forced vital capacity nationallicence MEF75%FVC : mid-expiratory flow at 75% of forced vital capacity nationallicence PFT : pulmonary function testing nationallicence sRAW : specific airway resistance nationallicence T : total amount of radioactivity in the cartridge nationallicence TI : Technosphere Insulin nationallicence tmax : time to maximum observed drug concentration nationallicence Tndel : total amount of 99mTc-TI inhalation powder that is not delivered to the body nationallicence Cassidy James MannKind Corporation, Valencia, California, USA aut Amin Nikhil MannKind Corporation, Valencia, California, USA aut Marino Mark MannKind Corporation, Valencia, California, USA aut Gotfried Mark College of Medicine University of Arizona and Pulmonary Associates, Phoenix, Arizona, USA aut Meyer Thomas Inamed Research GmbH, Gauting, Germany aut Sommerer Knut Inamed Research GmbH, Gauting, Germany aut Baughman Robert MannKind Corporation, Valencia, California, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2157-2164 0724-8741 28:9<2157 2011 28 11095 https://doi.org/10.1007/s11095-011-0443-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0443-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cassidy James MannKind Corporation, Valencia, California, USA aut NATIONALLICENCE 700 1- Amin Nikhil MannKind Corporation, Valencia, California, USA aut NATIONALLICENCE 700 1- Marino Mark MannKind Corporation, Valencia, California, USA aut NATIONALLICENCE 700 1- Gotfried Mark College of Medicine University of Arizona and Pulmonary Associates, Phoenix, Arizona, USA aut NATIONALLICENCE 700 1- Meyer Thomas Inamed Research GmbH, Gauting, Germany aut NATIONALLICENCE 700 1- Sommerer Knut Inamed Research GmbH, Gauting, Germany aut NATIONALLICENCE 700 1- Baughman Robert MannKind Corporation, Valencia, California, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2157-2164 0724-8741 28:9<2157 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer