Pharmacokinetics and pharmacodynamics of intranasal insulin administered to patients with type 1 diabetes: a preliminary study.
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.
Leary
Andrew C
AC
Department of Pharmacology and Therapeutics, National University of Ireland and Shandon Clinic, Cork, Ireland. andrew.leary@shandonclinic.ie
Stote
Robert M
RM
Cussen
Kathleen
K
O'Brien
Jackie
J
Leary
William P
WP
Buckley
Brendan
B
D000281:Administration, Intranasal; D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008657:Metabolic Clearance Rate; D010919:Placebos
D001786:Blood Glucose; D007328:Insulin; D010919:Placebos