Inhaled Insulin Using the AERx Insulin Diabetes Management System in Healthy and Asthmatic Subjects
- Robert R. Henry, MD1,
- Sunder R.D. Mudaliar, MD1,
- William C. Howland III, MD2,
- Neelima Chu, MD1,
- Dennis Kim, MD1,
- Bob An, PHD3 and
- Rickey R. Reinhardt, MD, PHD3
- 1VA San Diego Healthcare System, Section of Diabetes/Endocrinology, San Diego, California
- 2HealthQuest Research, Austin, Texas
- 3Novo Nordisk Pharmaceuticals, Princeton, New Jersey
OBJECTIVE—The AERx insulin Diabetes Management System (AERx iDMS) (Aradigm, 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 [ FEV1] 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 = 0.013), whereas no difference was observed for maximum concentration (Cmax) 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 = 0.007). Asthmatic subjects had greater intrasubject variations in insulin AUC(0–360 min) and Cmax values than healthy subjects, but similar variations in glucose AOC(0–360 min). No significant changes in FEV1, forced vital capacity (FVC), and FEV1/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.
- AERx iDMS, AERx insulin Diabetes Management System
- AOC, area over the curve
- AUC, area under the curve
- Cmax, maximum concentration
- CV, coefficient of variation
- ECG, electrocardiogram
- FEV1, forced expiratory volume during the first second
- FVC, forced vital capacity
- LS, least square
- MS, most square
- PD, pharmacodynamics
- PFT, pulmonary function test
- PK, pharmacokinetics
- Tmax, time at which concentration is maximal
- URI, upper respiratory tract infection
Address correspondence and reprint requests to Robert R. Henry, Section of Diabetes/Endocrinology, VA San Diego Healthcare System, 3350 La Jolla Village Dr. (111G), San Diego, CA 92161. E-mail:.
Received for publication 8 August 2002 and accepted in revised form 4 December 2002.
D.K. is employed by and holds stock in Amylin Pharmaceuticals.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
- DIABETES CARE