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.
RCT Entities:
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.