title: Inhaled insulin using the AERx Insulin Diabetes Management System in healthy and asthmatic subjects.
abstract: 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.
  
  
  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 = 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 = 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.
authors.affiliation: VA San Diego Healthcare System, Section of Diabetes/Endocrinology, San Diego, California 92161, USA. rrhenry@vapop.ucsd.edu
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.forename: Sunder R D
authors.initials: SR
authors.lastname: Mudaliar
authors.forename: William C
authors.initials: WC
authors.lastname: Howland
authors.forename: Neelima
authors.initials: N
authors.lastname: Chu
authors.forename: Dennis
authors.initials: D
authors.lastname: Kim
authors.forename: Bob
authors.initials: B
authors.lastname: An
authors.forename: Rickey R
authors.initials: RR
authors.lastname: Reinhardt
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000378:metabolism*; D001786:Blood Glucose / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin