INTRATRACHEAL DELIVERY OF INSULIN ABSORPTION FROM SOLUTION AND AEROSOL BY RAT LUNG

In this study, we investigated the dynamics of insulin absorption from the lung with reference to bioavailability. Human insulin in 10 mul of aqueous solution and an insulin aerosol were administered into the exposed trachea of anesthetized rats. Blood samples were collected from the jugular vein at specified intervals and the plasma concentration of insulin was determined by an EIA. The relative bioavailability of insulin after intratracheal administration in 10 mul of pH 7.0 isotonic phosphate buffer and pH 3.0 isotonic citrate buffer was 13 and 42%, respectively, of that obtained after subcutaneous administration. Although insulin absorption in the presence of surfactants such as glycocholate, surfactin, and Span 85 was 3-4-times greater than that without surfactants, the co-administration of EDTA and salicylate, which previously enhanced the absorption of rectally administered insulin, did not increase the intratracheal absorption of insulin. The concomitant administration of nafamostat, a protease inhibitor, produced modest effects. The relative bioavailability of insulin given as an intratracheal aerosol was similar to that after subcutaneous administration. These observations indicate that the intratracheal route may be useful for the delivery of insulin.