Scientific Publications

Feb 2006, Vol. 8, No. 1: 81-88

Diabetes Technology & Therapeutics
Pharmacokinetics and Pharmacodynamics of Intranasal Insulin Administered to Patients with Type 1 Diabetes: A Preliminary Study

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., Exeter, New Hampshire.
Kathleen Cussen, M.Sc.
Shandon Clinic, Cork, Ireland.
Jackie O'brien, R.N.
Shandon Clinic, Cork, Ireland.
William P. Leary, D.Sc.
Department of Pharmacology and Therapeutics, National University of Ireland and Shandon Clinic, Cork, Ireland.
Brendan Buckley, D.Phil.
Department of Pharmacology and Therapeutics, National University of Ireland, Cork, Ireland.

Background: The pharmacokinetics and pharmacodynamics of a Bentley Pharmaceuticals (Exeter, NH) proprietary insulin formulation designed for intranasal administration were studied in patients with type 1 diabetes, using subcutaneous insulin or placebo as comparator.
Methods: Seven fasting volunteer patients with type 1 diabetes (five men, two women; body mass index 23.54 ± 1.32 kg/m2) received up to four doses of medication (placebo, subcutaneous insulin, or intranasal insulin) at least 3 days apart. Serum insulin and plasma glucose were measured in the 5-h period after dosing.

Results: The relative bioavailability of intranasal insulin compared with subcutaneous insulin was 16.6–19.8% over 2 h and 14.0–19.8% over 5 h. The formulation was generally well tolerated. At doses of 25 IU and above, a rise in serum insulin levels accompanied by a decrease in plasma glucose was seen. Peak insulin levels were generally attained in 15–20 min and remained elevated for approximately 1 h; the resultant effect upon glucose peaked at 40 min and waned 1.5–2 h post-dosing. The effect was dose related. Mean peak insulin levels increased with dose escalation. As reported in other insulin studies, the inter-individual responsiveness to insulin was variable.

Conclusions: This intranasal formulation was generally well tolerated, and relatively well absorbed as demonstrated by a rapid rise in serum insulin level and concomitant reduction of plasma glucose levels.