MannKind Corporation, Valencia, California, USA.
Pharm Res. 2011 Sep;28(9):2157-64. doi: 10.1007/s11095-011-0443-4. Epub 2011 Apr 14.
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 (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.
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.
确定 Technosphere®胰岛素（TI）吸入粉的分布和沉积，以及肺部清除糠二酮哌嗪（FDKP；Technosphere 颗粒的主要成分）和胰岛素的速度。
使用 MedTone®吸入器给药后，立即通过伽马闪烁扫描定量测定吸附在 TI 上的（99m）锝的沉积和分布。在 TI 吸入粉给药后的第二个实验中，通过连续支气管肺泡灌洗（BAL）研究从肺部清除的情况，并对回收的液体进行 FDKP 和胰岛素检测。
吸入后，从吸入器发出的约 60%的放射性（吸附在 TI 上）被输送到肺部；其余发射剂量被吞下。FDKP 和胰岛素从肺上皮衬液（ELF）中的清除半衰期约为 1 小时。
通过 MedTone 吸入器给药的 TI 吸入粉在肺部均匀分布；初始药筒负荷的约 40%到达肺部。胰岛素和 FDKP 从肺部迅速清除，主要通过吸收进入体循环。从两个成分的连续 BAL 液测量估计，从肺 ELF 的终末清除半衰期约为 1 小时。由于有一个过夜的冲洗期，慢性给药时的蓄积潜力很小。
