Diabetes Technology
& Therapeutics
Pharmacokinetics and Pharmacodynamics of Intranasal Insulin Administered
to Healthy Subjects in Escalating Doses
Dr. Andrew
C. Leary, M.D. Department of Pharmacology and Therapeutics, National University of
Ireland; and Shandon Clinic, Cork, Ireland. Robert M. Stote, M.D. Bentley Pharmaceuticals, Inc., North Hampton, New Hampshire. H.J. Breedt, B.Sc.(Hons) Shandon Clinic, Cork, Ireland. Jackie O'brien, R.N. Shandon Clinic, Cork, Ireland. Brendan Buckley, D.Phil. Department of Pharmacology and Therapeutics, National University of
Ireland, Cork, Ireland.
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-µL 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.