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The effect of terbutaline on the absorption of pulmonary administered insulin in subjects with asthma

Petersen, Astrid H.; Korsatko, Stefan; Kohler, Gerd; Wutte, Andrea; Olschewski, Horst; Sparre, Thomas; Rastam, Jacob; Wollmer, Per LU and Pieber, Thomas R. (2010) In British Journal of Clinical Pharmacology 69(3). p.271-278
Abstract
center dot People with mild and moderate asthma have been shown to absorb less inhaled insulin than healthy subjects. center dot 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 center dot This study is the first to show that in people with asthma, reduction of bronchoconstriction leads to increased absorption of inhaled insulin. center dot 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... (More)
center dot People with mild and moderate asthma have been shown to absorb less inhaled insulin than healthy subjects. center dot 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 center dot This study is the first to show that in people with asthma, reduction of bronchoconstriction leads to increased absorption of inhaled insulin. center dot 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 (C-max) 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 C-max 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pharmacodynamics, insulin absorption, drug safety, aerosol, asthma, pharmacokinetics
in
British Journal of Clinical Pharmacology
volume
69
issue
3
pages
271 - 278
publisher
John Wiley & Sons
external identifiers
  • wos:000274438500008
  • scopus:76649105156
ISSN
1365-2125
DOI
10.1111/j.1365-2125.2009.03573.x
language
English
LU publication?
yes
id
59c37261-3d32-4e7b-aa55-4d84dd862a33 (old id 1568972)
date added to LUP
2010-03-17 10:05:14
date last changed
2018-05-29 10:36:37
@article{59c37261-3d32-4e7b-aa55-4d84dd862a33,
  abstract     = {center dot People with mild and moderate asthma have been shown to absorb less inhaled insulin than healthy subjects. center dot 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 center dot This study is the first to show that in people with asthma, reduction of bronchoconstriction leads to increased absorption of inhaled insulin. center dot 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 (C-max) 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 C-max 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.},
  author       = {Petersen, Astrid H. and Korsatko, Stefan and Kohler, Gerd and Wutte, Andrea and Olschewski, Horst and Sparre, Thomas and Rastam, Jacob and Wollmer, Per and Pieber, Thomas R.},
  issn         = {1365-2125},
  keyword      = {pharmacodynamics,insulin absorption,drug safety,aerosol,asthma,pharmacokinetics},
  language     = {eng},
  number       = {3},
  pages        = {271--278},
  publisher    = {John Wiley & Sons},
  series       = {British Journal of Clinical Pharmacology},
  title        = {The effect of terbutaline on the absorption of pulmonary administered insulin in subjects with asthma},
  url          = {http://dx.doi.org/10.1111/j.1365-2125.2009.03573.x},
  volume       = {69},
  year         = {2010},
}