Insulin lung deposition and clearance following Technosphere® insulin inhalation powder administration

Pharm Res. 2011 Sep;28(9):2157-64. doi: 10.1007/s11095-011-0443-4. Epub 2011 Apr 14.


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.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Inhalation
  • Adult
  • Bronchoalveolar Lavage Fluid / chemistry
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics
  • Drug Delivery Systems / instrumentation
  • Drug Delivery Systems / methods
  • Female
  • Fumarates / analysis
  • Fumarates / pharmacokinetics
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacokinetics*
  • Insulin / administration & dosage*
  • Insulin / chemistry
  • Insulin / pharmacokinetics*
  • Lung / diagnostic imaging
  • Lung / metabolism*
  • Male
  • Metabolic Clearance Rate
  • Nebulizers and Vaporizers
  • Particle Size
  • Piperazines / analysis
  • Piperazines / pharmacokinetics
  • Powders
  • Radionuclide Imaging
  • Sodium Pertechnetate Tc 99m / chemistry
  • Tissue Distribution


  • Drug Carriers
  • Fumarates
  • Hypoglycemic Agents
  • Insulin
  • Piperazines
  • Powders
  • Sodium Pertechnetate Tc 99m
  • 3,6-bis(N-fumaryl-N(n-butyl)amino)-2,5-diketopiperazine