title: Effect of upper respiratory tract infection on AIR inhaled insulin pharmacokinetics and glucodynamics in healthy subjects.
abstract: The suitability of employing AIR Inhaled Insulin (AIR Insulin; AIR is a registered trademark of Alkermes) during acute upper respiratory tract infection (URI) has not been determined. Twenty-one healthy, non-diabetic subjects were enrolled in a single-sequence, two-period, euglycemic clamp study. Subjects received a single 12 U-equivalent dose of AIR Insulin before rhinovirus (RV16) inoculation and during symptomatic infection. Spirometry was used to evaluate pulmonary safety. AIR Insulin exposure (the area under the immunoreactive insulin (IRI) concentration vs time curve from time zero until the IRI concentrations returned to the predose baseline value (AUC(0-t'))) and glucodynamic response (total amount of glucose infused (G(tot))) were comparable before and during RV infection (AUC(0-t') 46,300 vs 52,600 pmol min/l, P=0.21; G(tot) 61,800 vs 68,700 mg, P=0.42, respectively). Variability of pharmacokinetic and pharmacodynamic parameters did not change during URI; either did the number or intensity of adverse events. No significant change in forced expiratory volume or forced vital capacity was observed following AIR Insulin administration or during URI. The AIR Insulin system provides similar pharmacokinetic and glucodynamic responses under conditions of an experimentally induced RV infection and is regarded as suitable for use in diabetic patients during URIs.
authors.affiliation: Department of Pediatrics, University of Wisconsin Medical School, Madison, Wisconsin, USA. gern@medicine.wisc.edu
authors.forename: J E
authors.initials: JE
authors.lastname: Gern
authors.forename: C K
authors.initials: CK
authors.lastname: Stone
authors.forename: M
authors.initials: M
authors.lastname: Nakano
authors.forename: D B
authors.initials: DB
authors.lastname: Muchmore
authors.forename: A
authors.initials: A
authors.lastname: de la Peña
authors.forename: S
authors.initials: S
authors.lastname: Park
authors.forename: A
authors.initials: A
authors.lastname: Suri
authors.forename: F
authors.initials: F
authors.lastname: Tibaldi
authors.forename: D
authors.initials: D
authors.lastname: Soon
authors.forename: W W
authors.initials: WW
authors.lastname: Busse
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects*; D005541:Forced Expiratory Volume; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010850:Picornaviridae Infections / Q000378:metabolism* / Q000503:physiopathology; D012141:Respiratory Tract Infections / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D013147:Spirometry; D014797:Vital Capacity
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin