OBJECTIVE: This study evaluated pharmacokinetic and glucodynamic responses to AIR inhaled insulin relative to subcutaneous insulin lispro, safety, pulmonary function, and effects of salbutamol coadministration. RESEARCH DESIGN AND METHODS: Healthy, mildly asthmatic, and moderately asthmatic subjects (n = 13/group, aged 19-58 years, nonsmoking, and nondiabetic) completed this phase I, open-label, randomized, crossover euglycemic clamp study. Subjects received 12 units equivalent AIR insulin or 12 units subcutaneous insulin lispro or salbutamol plus AIR insulin (moderate asthma group only) before the clamp. RESULTS:AIR insulin exposure was reduced 34 and 41% (both P < 0.01) in asthmatic subjects (area under the curve(0-t'), 24.0 and 21.1 nmol x min x l(-1) in mild and moderate asthma subjects, respectively) compared with healthy subjects (35.2 nmol x min x l(-1)), respectively. Glucodynamic (G) effects were similar in healthy and mildly asthmatic subjects (G(tot) = 38.7 and 23.4 g, respectively; P = 0.16) and were reduced in moderately asthmatic subjects (G(tot) = 10.7 g). Salbutamol pretreatment (moderately asthmatic subjects) improved bioavailability. AIR insulin had no discernable effect on pulmonary function. AIR insulin adverse events (cough, headache, and dizziness) were mild to moderate in intensity and have been previously reported or are typical of studies involving glucose clamp procedures. CONCLUSIONS: This study suggests that pulmonary disease severity and asthma treatment status influence the metabolic effect of AIR insulin in individuals with asthma but do not affect AIR insulin pulmonary safety or tolerability. In view of the potential interactions between diabetes treatment and pulmonary status, it is prudent to await the results of ongoing clinical trials in diabetic patients with comorbid lung disease before considering the use of inhaled insulin in such patients.
RCT Entities:
OBJECTIVE: This study evaluated pharmacokinetic and glucodynamic responses to AIR inhaled insulin relative to subcutaneous insulin lispro, safety, pulmonary function, and effects of salbutamol coadministration. RESEARCH DESIGN AND METHODS: Healthy, mildly asthmatic, and moderately asthmatic subjects (n = 13/group, aged 19-58 years, nonsmoking, and nondiabetic) completed this phase I, open-label, randomized, crossover euglycemic clamp study. Subjects received 12 units equivalent AIR insulin or 12 units subcutaneous insulin lispro or salbutamol plus AIR insulin (moderate asthma group only) before the clamp. RESULTS: AIR insulin exposure was reduced 34 and 41% (both P < 0.01) in asthmatic subjects (area under the curve(0-t'), 24.0 and 21.1 nmol x min x l(-1) in mild and moderate asthma subjects, respectively) compared with healthy subjects (35.2 nmol x min x l(-1)), respectively. Glucodynamic (G) effects were similar in healthy and mildly asthmatic subjects (G(tot) = 38.7 and 23.4 g, respectively; P = 0.16) and were reduced in moderately asthmatic subjects (G(tot) = 10.7 g). Salbutamol pretreatment (moderately asthmatic subjects) improved bioavailability. AIR insulin had no discernable effect on pulmonary function. AIR insulin adverse events (cough, headache, and dizziness) were mild to moderate in intensity and have been previously reported or are typical of studies involving glucose clamp procedures. CONCLUSIONS: This study suggests that pulmonary disease severity and asthma treatment status influence the metabolic effect of AIR insulin in individuals with asthma but do not affect AIR insulin pulmonary safety or tolerability. In view of the potential interactions between diabetes treatment and pulmonary status, it is prudent to await the results of ongoing clinical trials in diabeticpatients with comorbid lung disease before considering the use of inhaled insulin in such patients.
Authors: Astrid H Petersen; Stefan Korsatko; Gerd Köhler; Andrea Wutte; Horst Olschewski; Thomas Sparre; Jacob Råstam; Per Wollmer; Thomas R Pieber Journal: Br J Clin Pharmacol Date: 2010-03 Impact factor: 4.335