The effect of physiological manoeuvres on the absorption of inhaled nedocromil sodium.

Köhler

Korsatko

et al. 2007

Brit J Clinical Pharma

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. AIMSTo investigate the effect of moderate exercise on the absorption of inhaled insulin. METHODSA 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 )). RESULTSThe 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 (Cmax) increased by 32% for EX0 and 35% for EX30 (both P < 0.01) compared with NOEX, while the time to Cmax was 31 min faster for EX0 (P < 0.01), but not significantly different after EX30, compared with NOEX.

Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The effect of exercise on the absorption of inhaled human insulin in healthy volunteers

Köhler

Korsatko

et al. 2007

Brit J Clinical Pharma

“…At all three occasions, the bronchodilator (1.0 mg terbutaline in turbuhaler®; Astra‐Zeneca GmbH, Wedel, Germany) was administered in two inhalations. The pulmonary function test to measure FEV 1 reversibility was performed 15 min after administration of the bronchodilator, when a near‐maximal bronchodilator effect of terbutaline was to be expected [16, 17], and 15 min before administration of inhaled insulin, thereby minimizing any effect of the pulmonary function manoeuvres that have been shown to effect absorption of inhaled substances [18, 19].…”

Section: Methodsmentioning

confidence: 99%

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

Korsatko

Köhler

et al. 2010

Brit J Clinical Pharma

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. AIMTo investigate the effect of prior administration of a bronchodilator on the absorption of inhaled insulin in people with asthma treated with inhaled corticosteroids. METHODSA 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). RESULTSPrior 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). CONCLUSIONSIn 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.

“…Increased absorption/absorption rate as an effect of exercise is well known for other inhaled substances such as technetium 99m-labeled diethylene triamine penta-acetic acid (13,14), nedocromil sodium (15), and terbutaline (16). In a recent preliminary study in healthy volunteers who exercised after inhalation of insulin via a nebulizer system, we saw clinically relevant effects of exercise (17) and thus warranted further investigations in people with type 1 diabetes who respond differently to exercise than healthy people (18).…”

mentioning

confidence: 99%

The Effect of Exercise on the Absorption of Inhaled Human Insulin via the AERx Insulin Diabetes Management System in People With Type 1 Diabetes

Köhler²,

Korsatko³

et al. 2007

Diabetes Care

OBJECTIVE -This study investigated the effect of moderate exercise on the absorption of inhaled insulin via the AERx insulin diabetes management system (iDMS). RESEARCH DESIGN AND METHODS -In this randomized, open-label, four-period, crossover, glucose clamp study 23 nonsmoking subjects with type 1 diabetes received a dose of 0.19 units/kg inhaled human insulin followed in random order by either 1) no exercise (NOEX group) or 30 min exercise starting, 2) 30 min after dosing (EX30), 3) 120 min after dosing (EX120), or 4) 240 min after dosing (EX240).RESULTS -Exercise changed the shape of the free plasma insulin curves, but compared with the NOEX group the area under the curve for free plasma insulin (AUC ins ) for the first 2 h after the start of exercise was unchanged for EX30 and EX240, while it was 15% decreased for EX120 (P Ͻ 0.01). The overall insulin absorption during 6 and 10 h after dosing was 13% decreased for EX30 (P Ͻ 0.005), 11% decreased for EX120 (P Ͻ 0.01), and unchanged for EX240. Exercise did not influence the maximum insulin concentration (C max ), while the time to C max was 22 min earlier for EX30 (P ϭ 0.04). The AUC for the glucose infusion rate (AUC GIR ) for 2 h after the start of exercise increased by 58% for EX30, 45% for EX120, and 71% for EX240 (all P Ͻ 0.02) compared with the NOEX group.CONCLUSIONS -Thirty minutes of moderate exercise led to unchanged or decreased absorption of inhaled insulin via AERx iDMS and faster C max for early exercise. Thus, patients using AERx iDMS can adjust insulin dose as usual independent of time of exercise, but they should be aware of the faster effect if exercising early after dosing.