Insulin pharmacokinetics following dosing with Technosphere insulin in subjects with chronic obstructive pulmonary disease

AbstractObjectives:Insulin exposure after inhalation has been reported to be altered significantly in subjects with chronic obstructive pulmonary disease (COPD). In this study, the rate and extent of insulin exposure was compared in healthy volunteers and subjects with COPD following administration of Technosphere Insulin (TI), a dry powder insulin formulation for pulmonary delivery.Methods:Insulin pharmacokinetics were evaluated in an open-label, single-dose, hyperinsulinemic-euglycemic glucose clamp study in 19 nondiabetic, nonsmoking healthy subjects (mean age [±SD] = 50.9 ± 14.1 years, body mass index = 29.1 ± 3.5 kg/m2, forced expiratory volume in 1 second (FEV1) = 3.52 ± 1.02 L) and 17 nondiabetic subjects with mild-to-moderate COPD (mean age = 60.0 ± 9.0 years, body mass index = 28.5 ± 5 kg/m2, FEV1 = 2.56 ± 0.83 L). Subjects received a single 30-U dose of TI. Serial blood samples were obtained for insulin and C-peptide determination through 480 min after dosing. Insulin concentrations were adjuste...