THE PHARMACOKINETICS OF PULMONARY NEBULIZED INSULIN AND ITS EFFECT ONGLUCOSE-TOLERANCE IN STREPTOZOTOCIN-INDUCED DIABETIC RABBITS

The bioavailability of insulin administered by a modified mini-mist ai r compressor fitted nebulizer into the pulmonary route of streptozotoc in-induced diabetic rabbits was investigated. The glucose tolerance wa s measured by an intravenous glucose tolerance test (IVGTT) prior and after the induction of diabetes to establish diabetic control for each rabbit. An increase in nebulized dose concentration from 2 to 6 U/kg. rbw (rabbit body weight) was found to produce proportional dose respo nse showed by the increased values of the fractional glucose clearance (FGC) from 3.8 +/- 0.45 to 10 +/- 1.4, the increased values in serum insulin peaks above the basal levels from 115 +/- 27 to 330 +/- 46 mu U ml(-1) with corresponding AUCs between 105 +/- 26 and 347 +/- 47 mu U h ml(-1), and also the increased rabbits glucose tolerability in ter m of percentage total reduction in plasma glucose (%TRPG(0-2h) between 21.75% and 43.17% compared with a value of 14.61% for diabetic contro l rabbits. The rabbits' glucose tolerability after pulmonary administr ation was found to reach a value of up to 65% of comparable subcutaneo usly insulin dose; however, the AUC serum/insulin time profile of the former was about 50% of that of the latter. The results also demonstra ted that insulin delivered by the nebulizer produced more rapid peaks serum insulin and minimum serum glucose concentrations in contrast to the slower peaks produced by subcutaneously administered insulin.