Pharmacokinetics and pharmacodynamics of intranasal insulin administered to healthy subjects in escalating doses.

Background: This exploratory study examined the pharmacokinetics and pharmacodynamics of a Bentley Pharmaceuticals, Inc. (North Hampton, NH) proprietary insulin formulation utilizing CPE-215 technology designed for intranasal administration.

Methods: Eight fasting healthy volunteers (four men, four women; body mass index, 23.6 +/- 1.7 kg/m2) received up to four doses of intranasal insulin at least 1 week apart. Serum insulin, C-peptide, and plasma glucose were measured in the 4-h period following administration.

Results: At doses of 18.75 IU and above, a rise in serum insulin levels accompanied by a decrease in plasma glucose and serum C-peptide levels was seen. Insulin levels peaked in 10-20 min and remained elevated for approximately 1 h, and the resultant hypoglycaemic effect peaked at 40 min and returned to normal 1.5-2 h post-dosing. At 25 IU (n = 11 doses; eight subjects with three replicates), there was a mean fall in plasma glucose of 20.49%; a greater fall in plasma glucose was seen with higher insulin doses. In addition, mean peak insulin levels increased with dose escalation. For the 25 IU dose (a single 90-microL spray), the maximum measured insulin concentration was 19.52 +/- 9.28 mIU/L, and the area under the concentration-time curve from 0 to 4 h was 19.06 +/- 5.56 mIU/L/h. Three subjects with repeated 25 IU doses demonstrated similarly reproducible peaks for maximum measured insulin concentration and for plasma glucose reductions. As seen with other insulin studies, the inter-individual responsiveness to insulin was variable.

Conclusions: This intranasal formulation was generally well tolerated and demonstrated rapid onset of action and appropriate duration of action for the potential use in controlling postprandial hyperglycaemia.