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Insulin Lung Deposition and Clearance Following Technosphere® Insulin Inhalation Powder Administration



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.


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.


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.


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.

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AUC0–t :

area under the insulin concentration-time curve from 0 to time t


bronchoalveolar lavage


epithelial lining fluid of the lungs


fumaryl diketopiperazine

FEV1 :

forced expiratory volume in 1 s


inspiratory vital capacity


mid-expiratory flow at 25% of forced vital capacity


mid-expiratory flow at 50% of forced vital capacity


mid-expiratory flow at 75% of forced vital capacity


pulmonary function testing

sRAW :

specific airway resistance


total amount of radioactivity in the cartridge


Technosphere Insulin

tmax :

time to maximum observed drug concentration

Tndel :

total amount of 99mTc-TI inhalation powder that is not delivered to the body


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The authors extend their appreciation to Dr. Andreas Pfützner, University of Applied Sciences, Bingen, Germany, the principal investigator, and the staff at Inamed, Gauting, Germany, for the excellent conduct of the radiolabeled study; the research coordinators at Pulmonary Associates, Phoenix, AZ, USA, and the Endoscopy Department of John C. Lincoln North Mountain Hospital, Phoenix, AZ, USA, for conducting a quality bronchoscopy study; and the staffs at BARC, Lake Success, NY, USA (serum insulin), and QPS, Newark, DE, USA (serum and BAL FDKP and BAL insulin), for their excellent bioanalytical analysis of the samples; and Sungita Patel, who excelled as the clinical monitor for the BAL study.

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Correspondence to James P. Cassidy.

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Cassidy, J.P., Amin, N., Marino, M. et al. Insulin Lung Deposition and Clearance Following Technosphere® Insulin Inhalation Powder Administration. Pharm Res 28, 2157–2164 (2011).

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  • Afrezza®
  • fumaryl diketopiperazine
  • inhalation powder
  • insulin clearance
  • insulin lung disposition
  • Technosphere Insulin inhalation powder