Inhaled Insulin Using the AERx Insulin Diabetes Management System in Healthy and Asthmatic Subjects

Abstract

, Hayward, CA) delivers an aerosol of liquid human insulin to the deep lung for systemic absorption. This study examined the effects on pulmonary function, pharmacokinetics, and pharmacodynamics of inhaled insulin in asthmatic and nonasthmatic subjects without diabetes. RESEARCH DESIGN AND METHODS-A total of 28 healthy and 17 asthmatic (forced expiratory volume during the first second [FEV 1 ] 50 -80% of predicted value) subjects were enrolled in a two-part, open-label trial. To assess insulin pharmacokinetics and pharmacodynamics, a single inhalation dose of 1.57 mg (45 IU) was given on each of the 2 dosing days in part 1. A dose of 4.7 mg (135 IU) of insulin was inhaled in part 2 to assess effects on pulmonary function.RESULTS -Inhaled insulin showed area under the curve (AUC) (0 -360 min) values that were significantly greater for healthy subjects than for asthmatic subjects (P ϭ 0.013), whereas no difference was observed for maximum concentration (C max ) in the two groups. A greater reduction of serum glucose as indicated by area over the curve (AOC) (0 -360 min) was observed in healthy subjects (P ϭ 0.007). Asthmatic subjects had greater intrasubject variations in insulin AUC (0 -360 min) and C max values than healthy subjects, but similar variations in glucose AOC (0 -360 min) . No significant changes in FEV 1 , forced vital capacity (FVC), and FEV 1 /FVC were observed from pre-to postdose times, and there were no observed safety issues.CONCLUSIONS -After inhaling insulin using the AERx iDMS, asthmatic subjects absorbed less insulin than healthy subjects, resulting in less reduction of serum glucose. No effects on airway reactivity were observed. Diabetic patients with asthma may need to inhale more insulin than patients with normal respiratory function in order to achieve similar glycemic control. Diabetes Care 26:764 -769, 2003I ntensive insulin therapy has been demonstrated to reduce long-term complications in patients with type 1 and type 2 diabetes (1,2). When used as a mealtime insulin in a basal/bolus regimen, short-or rapid-acting insulin significantly improved posprandial glycemic control, with less incidence of hypoglycemia (3-7). Many patients object to multiple daily injection and therefore often receive a less-than-maximal benefit of insulin therapy.The AERx insulin Diabetes Management System (AERx iDMS) was developed by Aradigm (Hayward, CA) as a pulmonary drug delivery system for liquid formulations of insulin (8,9). The AERx iDMS produces a fine droplet aerosol (mass median aerodynamic diameter of ϳ2-3 m) from disposable insulin strips, by extruding a prepackaged solution through hundreds of laser-drilled holes in a single-use nozzle (10). The rapid onset of action of inhaled insulin is very similar to rapid-acting insulin analogs (11-13). The availability of a noninvasive delivery system that achieves rapid absorption of insulin into the circulation would be beneficial for administering mealtime insulin. Such a system would allow insulin therapy to more closely mimic the endogenous in...

Concept, Strategies, and Feasibility of Noninvasive Insulin Delivery

“…A study in healthy volunteers suggested that changes in the inhaled volume and depth of inspiration influenced pharmacokinetics of insulin delivered using this system (44). Upper respiratory tract infections do not seem to induce any clinically relevant changes in pharmacokinetics or pharmacodynamics (although t max is significantly reduced) (46), whereas the dose may need to be adjusted upward in asthmatics (47).…”

AIR Inhaled Insulin Versus Subcutaneous Insulin

“…Limited information has been published regarding the impact of asthma on inhaled insulin pharmacokinetic and/or glucodynamic parameters. Henry et al (16), using an aerosol of aqueous insulin, reported significantly reduced insulin exposure and reduced glucose effects in mild-tomoderate asthmatic subjects compared with a healthy group. In our study, mild and moderate asthma groups had similar reductions in inhaled insulin exposure, though differing glucose effects, relative to healthy subjects.…”

Controvérsias na associação entre diabetes mellitus tipo 1 e asma

“…Nos estudos iniciais, diabéticos asmáticos absorveram menos insulina por via inalatória, necessitando de doses maiores do que diabéticos sem asma para obterem controle da glicemia (57).…”