A new approach for insulin delivery via the pulmonary route: Design and pharmacokinetics in non-diabetic rabbits

Abstract

A mini-mist medication air compressor fitted nebulizer was used to deliver insulin in the form of a fine mist via the rabbit's pulmonary system. An insulin immune test was first performed in order to ensure the rabbit's respiratory compliance and then the bioavailability was examined as a function of insulin dose concentration and dose volume. An increase in dose concentration from 2 to 5 U kg − rbw was found to reduce the percentage minimum plasma glucose concentration (%MPGC) from 71 to 38% without affecting the time T required to attain these values (i.e., T%MPGC = 20 min). The values of the percentage total reduction in plasma glucose from 0 to 3 h (%TRPG 0–3h) were also found to increase from 15 to 37% as insulin concentration increased. On the other hand, an increase in dose volume from 1 to 3 ml did not lead to marked changes in both %MPGC and %TRPG(in0–3h) but did increase the value of T%MPGC from 20 to 50 min. Comparative study between pulmonary administered insulin (PAI and subcutaneously administered insulin (SAI) showed that the T%MPGC for PAI was about 1 5 of that for SAI with an acceptable duration for maintaining the lowering of plasma glucose. The apparent values of %MPGC and %TRPC 0–3h for PAI were about 36% of those for SAI and related to incomplete dose consumption as part of PAI was always retained inside the nebulizer. The corrected bioavailability for PAI was therefore calculated and found to be greater than 50% of that for SAI.