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- Petersen, AH, et al.
(författare)
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The effect of exercise on the absorption of inhaled human insulin in healthy volunteers
- 2008
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 65:2, s. 165-171
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Tidskriftsartikel (refereegranskat)abstract
- What is already known about this subject * Exercise is known to affect absorption of other inhaled substances, but so far there are no reports on the effect of exercise on the absorption of inhaled insulin in humans. What this paper adds * This report is the first to investigate the effect of exercise on the absorption of inhaled insulin. * In this study in healthy volunteers we found that exercise early after dosing increased absorption (15-20%) of inhaled insulin over the first 2 h after start of exercise, with an approximately 30% increase in maximal insulin concentration, and unchanged overall absorption. Aims To investigate the effect of moderate exercise on the absorption of inhaled insulin. Methods A single-centre, randomized, open-label, three-period cross-over trial was carried out in 12 nonsmoking healthy subjects. A dose of 3.5 mg inhaled human insulin was administered via a nebulizer and followed in random order by either 1) no exercise (NOEX), 2) 30 min exercise starting immediately after dosing (EX0), or 3) 30 min exercise starting 30 min after dosing (EX30). The study was carried out as a 10 h euglycaemic glucose clamp (90 mg dl(-1) (5.0 mmol l(-1))). Results The absorption of insulin over the first 2 h after start of exercise was 16% increased for EX0 (ratio (95%CI) 1.16 (1.04, 1.30), P = 0.01) and 20% increased for EX30 (1.20 (1.05, 1.36), P < 0.01), both compared with NOEX; the overall insulin absorption during 6 h and 10 h after dosing was not influenced by exercise. The maximum insulin concentration (C(max)) increased by 32% for EX0 and 35% for EX30 (both P < 0.01) compared with NOEX, while the time to C(max) was 31 min faster for EX0 (P < 0.01), but not significantly different after EX30, compared with NOEX. Conclusions A significant and clinically relevant increase of insulin absorption over the first 2 h after the beginning of exercise was observed. Until data from studies using the specific insulin inhalers exists, patients using inhaled insulin should be made aware of a potential increased absorption and higher concentration of insulin in connection with exercise.
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| 2. |
- Bondesson, Eva, et al.
(författare)
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Site of deposition and absorption of an inhaled hydrophilic solute
- 2007
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 63:6, s. 722-731
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Tidskriftsartikel (refereegranskat)abstract
- Aims To characterize the absorption kinetics and bioavailability of an inhaled hydrophilic solute deposited at various sites within the airways. Methods Nine healthy nonsmokers received one intravenous, one oropharyngeal and two pulmonary doses of technetium-99 m-labelled diethylene triamine pentaacetic acid (Tc-99m-DTPA) in an open and crossover fashion. Pulmonary doses were administered as nebulized large and fine droplet-sized aerosols by Pari and UltraVent nebulizers at fairly rapid and slow inhalation flows, respectively. Plasma concentration-time profiles and 24 h urinary excretion of radioactivity were determined. One dose of Tc-99m-labelled Nanocoll, as a marker of mucociliary clearance (MCC), was also administered by Pari for similar lung deposition as the Tc-99m-DTPA and followed by repeated chest gamma-imaging. Results Intrapulmonary deposition patterns of Tc-99m-DTPA differed significantly (the mean ratio of penetration index (Pari : UltraVent) was 76% with 95% CI 63%, 91%). However, no differences in rate or extent of Tc-99m-DTPA absorption were detected. Mean absorption time was 1.8 h (mean difference (Pari-UltraVent): -0.1 h with 95% CI -0.6 h, 0.3 h) and the bioavailability was 70% (mean ratio (Pari : UltraVent): 101% with 95% CI 90%, 115%). The pulmonary elimination half-life of Tc-99m-Nanocoll (8 h and 45 min) was significantly longer than that of Tc-99m-DTPA (less than 2 h). The oral bioavailability of Tc-99m-DTPA was estimated to be 3.1%. Conclusions The main elimination pathway of the inhaled hydrophilic solute Tc-99m-DTPA from the lungs is trans-epithelial absorption. Despite different intrapulmonary radioaerosol deposition patterns, as verified by gamma scintigraphy, no differences in Tc-99m-DTPA absorption kinetics or bioavailability were detected.
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| 3. |
- Petersen, Astrid H., et al.
(författare)
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The effect of terbutaline on the absorption of pulmonary administered insulin in subjects with asthma
- 2010
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 69:3, s. 271-278
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Tidskriftsartikel (refereegranskat)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.
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