A.H.P. present address: Novo Nordisk A/S, Bagsvaerd, Denmark.
The effect of terbutaline on the absorption of pulmonary administered insulin in subjects with asthma
Article first published online: 5 NOV 2009
© 2010 The Authors. Journal compilation © 2010 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 69, Issue 3, pages 271–278, March 2010
How to Cite
Petersen, A. H., Korsatko, S., Köhler, G., Wutte, A., Olschewski, H., Sparre, T., Råstam, J., Wollmer, P. and Pieber, T. R. (2010), The effect of terbutaline on the absorption of pulmonary administered insulin in subjects with asthma. British Journal of Clinical Pharmacology, 69: 271–278. doi: 10.1111/j.1365-2125.2009.03573.x
- Issue published online: 10 FEB 2010
- Article first published online: 5 NOV 2009
- Received 15 June 2009 Accepted22 October 2009
- drug safety;
- insulin absorption;
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• People with mild and moderate asthma have been shown to absorb less inhaled insulin than healthy subjects.
• In people with moderate asthma, the administration of a bronchodilator before inhalation of insulin has been shown to lead to increased uptake of inhaled insulin compared with no prior administration of bronchodilator.
WHAT THIS STUDY ADDS
• This study is the first to show that in people with asthma, reduction of bronchoconstriction leads to increased absorption of inhaled insulin.
• This study illustrates that due to the effect of terbutaline on glucose metabolism, the effect of insulin on plasma glucose is complex when terbutaline is administered concomitantly.
AIM To investigate the effect of prior administration of a bronchodilator on the absorption of inhaled insulin in people with asthma treated with inhaled corticosteroids.
METHODS A single-centre, randomized, open-label, two-period cross-over trial was carried out in 41 nondiabetic subjects with asthma treated with inhaled steroids, with reversible bronchoconstriction (Rev+; n= 25) or without reversible bronchoconstriction (Rev−; n= 16). A dose of 0.10 U kg−1 inhaled human insulin was administered on each dosing day with or without prior administration of the bronchodilator terbutaline (in random order).
RESULTS Prior administration of terbutaline led to a 44% increase in absorption of insulin over 6 h for the Rev+ group compared with no prior administration of bronchodilator [ratio (95% confidence interval) 1.44 (1.13, 1.82), P= 0.004], whereas no effect was seen for the Rev− or the whole group. The maximum insulin concentration (Cmax) increased by 34% for the Rev+ group (P = 0.018) and 17% for the whole group (P= 0.046), whereas no significant effect of prior terbutaline administration was seen for Rev−. The time to Cmax was not significantly different for the Rev+ group, whereas it was approximately 30% longer after bronchodilator administration for the Rev− group (P= 0.044) and the whole group (P= 0.032).
CONCLUSIONS In people with asthma and reversible bronchoconstriction, the administration of a bronchodilator prior to administration of inhaled insulin led to increased absorption of insulin, whereas no effect on insulin absorption in subjects without significant reversibility could be detected.