title: Young and elderly type 2 diabetic patients inhaling insulin with the AERx insulin diabetes management system: a pharmacokinetic and pharmacodynamic comparison.
abstract: The objective of this study was to compare the pharmacokinetics (PK), pharmacodynamics (PD), and safety of inhaled insulin delivered by the AERx iDMS in young and elderly patients with type 2 diabetes. Twenty-seven young (18-45 years, inclusive) and 28 elderly (>/= 65 years) type 2 diabetic patients were enrolled in this study. A single inhalation of 1.57 mg (45 IU, effect comparable to 6 s.c. units) of regular human insulin was administered to each patient on each of 2 dosing days, and blood samples were drawn up to 360 minutes postdosing to generate the PK/PD curves. AUC(0-360 min) and Cmax values of inhaled insulin were comparable between young and elderly subjects (p = 0.476 for AUC(0-360 min) and p = 0.414 for Cmax). However, the elderly group had significantly less glucose reduction, as indicated by plasma glucose AOC(0-360) (area over the curve) values (p = 0.011). The intrasubject variability of inhaled insulin using the AERx iDMS was similar for young and elderly subjects and was similar to what has previously been reported for soluble insulin administered subcutaneously. Inhaled insulin was well tolerated in these patients, and no changes in pulmonary function tests were observed. A single inhalation of insulin using the AERx iDMS demonstrated comparable insulin PK profiles between the elderly and young type 2 patients but less glucose reduction in the elderly. Based on these results, elderly diabetic patients may need to inhale more insulin than young patients to achieve similar glycemic control. Long-term clinical trials using the AERx device will be useful to study age-related differences.
authors.affiliation: VA San Diego Healthcare System, Section of Diabetes/Endocrinology, 3350 La Jolla Village Dr. (111G), San Diego, CA 92161, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.forename: Sunder
authors.initials: S
authors.lastname: Mudaliar
authors.forename: Neelima
authors.initials: N
authors.lastname: Chu
authors.forename: Dennis
authors.initials: D
authors.lastname: Kim
authors.forename: Debra
authors.initials: D
authors.lastname: Armstrong
authors.forename: Trent T
authors.initials: TT
authors.lastname: Davis
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; D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007328:Insulin / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007328:Insulin