TIME-ACTION PROFILE OF INHALED INSULIN

We compared the pharmacodynamics of insulin after inhalation of 99 U m icrocrystalline solid insulin and subcutaneous injection of 10 U regul ar insulin and intravenous injection of 5 U regular insulin. The time- action profiles of the three insulin administrations were studied in 1 1 healthy volunteers using the euglycaemic glucose clamp technique. Th e insulins were administered to each volunteer on three separate occas ions in random order. Onset of action, assessed as glucose infusion ra te, after insulin inhalation was substantially more rapid than after s ubcutaneous injection and half-maximal action was reached earlier (31 +/- 17 vs 54 +/- 12 min; p < 0.001). Maximal metabolic response was re ached earlier after insulin inhalation in comparison to subcutaneous i njection (108 +/- 49 vs 147 +/- 53 min; p < 0.001). The maximal glucos e infusion rate after inhalation of insulin was lower than after subcu taneous insulin injection (6.2 +/- 2.4 vs 9.1 +/- 2.5 mg kg(-1) min(-1 ); p < 0.001). The glucose infusion rates in the first 60 min after in halation were significantly greater than after insulin injection (area under the glucose infusion rate curve: 0.23 +/- 0.12 vs 0.13 +/- 0.08 g kg(-1) 60 min(-1); p < 0.001). However, the total metabolic effect after inhalation was significantly lower than after insulin injection (1.44 +/- 0.68 vs 1.90 +/- 0.47 g kg(-1) 360 min(-1); p < 0.001). Rela tive effectiveness of inhaled insulin calculated with regard to the da ta from the intravenous insulin application was 9.5 +/- 4.1 % and of t he subcutaneous insulin application was 7.6 +/- 2.9 %. With its rapid onset of action, inhaled insulin might have potential for clinical use .