AIR Insulin Capsules of Different Dose Strengths May Be Combined to Yield Equivalent Pharmacokinetics and Glucodynamics

Abstract

Background:

In order to assess pharmacokinetic (PK) and glucodynamic (GD) attributes relevant to the end user of an inhaled insulin, this study examined the exposure and GD effect of doses of AIR^® inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) by combining capsules of different strengths in healthy subjects.

Methods:

Fifty-nine healthy, nonsmoking, male or female subjects with normal pulmonary function were enrolled in an open-label, randomized, crossover study. Subjects underwent up to five euglycemic glucose clamp procedures, separated by 5–18 days. The five AIR insulin treatments tested included one 6 unit-equivalent (U-eq) capsule containing 2.6 mg of insulin, three 2 U-eq (0.9 mg) capsules (2.7 mg total), one 10 U-eq (3.9 mg) capsule, one 6 U-eq capsule plus two 2 U-eq capsules (4.4 mg total), and two 10 U-eq capsules (7.8 mg total). Samples for PK and GD assessments were taken up to 10 h post-dose.

Results:

Based on both PK (area under the curve from time 0 to time of return to baseline and maximum concentration) and GD (total amount of glucose infused and maximum glucose infusion rate) responses, administration of a 6 U-eq capsule was equivalent to three 2 U-eq capsules; 90% confidence intervals for the ratios were contained within the interval (0.8, 1.25). Similarly, both overall exposure and glucodynamic response after administration of a 10 U-eq capsule were comparable to the 6 U-eq plus two 2 U-eq capsule combination. AIR insulin exhibited PK dose proportionality and dose-dependent increases in GD responses over the 2.6–7.8 mg dose range.

Conclusions:

AIR insulin exhibited dose strength interchangeability and dose proportionality after single-dose administration in healthy subjects.