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

To determine distribution and deposition of Technosphere(A (R)) 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 (99m)pertechnetate adsorbed onto TI immediately after administration using the MedToneA (R) 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, similar to 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 similar to 1 hour. TI inhalation powder administered via the MedTone inhaler was uniformly distributed throughout the lungs; similar to 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 similar to 1 hour. Since there is an overnight washout period, the potential for accumulation on chronic administration is minimal.