Effects of different durations of breath holding after inhalation of insulin using the AERx ® insulin diabetes management system

Abstract

Background: The AERx ® insulin diabetes management system (iDMS) is a new technology for the administration of insulin by inhalation. Objective: This study assessed the effects of different durations of breath holding (0, 3, and 10 seconds after inhalation) on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of insulin. Methods: This was an open-label, randomized, 3-period crossover study in which healthy subjects received a single inhalation of 45 IU regular human insulin followed by breath holding for 0, 3, and 10 seconds on 3 separate study days. Blood levels of insulin and glucose were assessed for 6 hours. Results: Twenty-one healthy subjects (8 men, 13 women; mean [SD] age, 32.1 [6.9] years; mean body mass index, 24.8 [3.2] kg/m 2) took part in the study. No significant differences were observed in any PK or PD parameter with the 3 durations of breath holding. Values for mean serum insulin area under the curve from 0 to 360 minutes were 8218, 8244, and 8404 μU/mL·min for the 0-, 3-, and 10-second durations of breath holding, respectively. Mean maximum insulin concentrations were a respective 44.9, 44.2, and 45.5 μU/mL. Values for mean plasma glucose area over the curve and below baseline from 0 to 360 minutes were a respective 3512, 4033, and 3708 mg/dL·min. Pairwise comparisons of serum insulin and plasma glucose concentrations showed no significant changes with the different durations of breath holding. Few adverse events were observed. Conclusions: The duration of breath holding after a single inhalation of insulin using the AERx iDMS had no significant effect on the PK or PD parameters of insulin. On the basis of the results in these healthy subjects, breath holding may not be necessary after inhalation of insulin using the AERx iDMS.