胰岛素气雾剂经大鼠肺部给药的生物利用度

目的　研究胰岛素(INS)经大鼠肺部给药后的生物利用度。方法　制备了含抛射剂的两相INS气雾剂，并用HPLC方法测定其每揿剂量。通过经口吸入及气管内给药两种途径将INS气雾剂导入大鼠肺内，用葡萄糖氧化酶法及放射免疫法分别测定了血清葡萄糖和INS水平，并计算其药理及药物的相对生物利用度。结果　两种剂量的INS气雾剂的每揿剂量分别为0.39 u及1.45 u。在两种剂量下，经口吸入和气管内给药在不同剂量下均呈现显著的降血糖作用及增加体内血清INS水平。在低剂量条件下，经口吸入及气管内给药的INS药物相对生物利用度分别达到24.3%和25.7%。结论　INS气雾剂经肺吸收后能达到较高的生物利用度。

BIOAVAILABILITIES OF INSULIN AEROSOL BY PULMONARY DELIVERY TO RATS

AIM To study the bioavailabilities of insulin (INS) aerosol given by pulmonary route to rats. METHODS Two phase INS aerosol in propellant system was prepared and the amount of insulin delivered per actuation was determined by HPLC method. INS aerosol was delivered by oral inhalation or intratracheal administration to rats. Blood glucose levels and serum INS concentrations were examined by glucose oxidase method and radioimmunoassay, respectively. The relative bioavailabilities were then calculated. RESULTS By HPLC determination, the amount of insulin per actuation of two different doses of INS aerosol was 0 39 u for low dose and 1 45 u for high dose. When delivered to rats, INS aerosol significantly reduced blood glucose level and increased serum INS concentrations by inhalation as well as intratracheal delivery at low or high doses. The relative bioavailability of the drug reached 24 3% by inhalation and 25 7% by intratracheal delivery at low dose. CONCLUSION Results indicated that INS aerosol showed higher bioavailability when given pulmonarily to rats.