The Protective Effect of Salbutamol Inhaled Using Different Devices on Methacholine Bronchoconstriction

Giannini, D; Franco, Antonella Di; Bacci, Elena; Dente, Federico L.; Taccola, M; Vagaggini, Barbara; Paggiaro, Pierluigi

doi:10.1378/chest.117.5.1319

Cited by 22 publications

(7 citation statements)

References 24 publications

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“…Inputs for simulations included between‐ and within‐subject variances of 2.5 and 0.5, respectively (log 2 [PC 20 FEV 1 ] scale). This within‐subject variance is near the lower end of the range observed in existing publications (Table ) . Treatment effect for each albuterol dose considered in this study was obtained based on a study by Parameswaran et al .…”

Section: Methodsmentioning

confidence: 72%

“…Although work presented here focuses on the importance of choice of study design, within‐subject variance continues to be a critical factor in determining sample size. Within‐subject variance observed in prior work ranged from 0.130 to 1.887 (Table ) . Corresponding sample size estimates ranged from 12 to 130 subjects to achieve 80% power (assuming the FDA‐recommended 3‐by‐1 study design and the simulation inputs for dose effects and between‐subject variance listed above).…”

Section: Discussionmentioning

confidence: 99%

“…Inputs for Monte Carlo simulations presented here were selected based on published studies . Log 2 [PC 20 FEV 1 ] was used as the dependent variable.…”

Section: Methodsmentioning

confidence: 99%

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Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short‐Acting β‐Agonist Formulations

Zeng

Singh

Wang

et al. 2017

The Journal of Clinical Pharma

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Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3‐by‐1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration–recommended 3‐by‐1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3‐by‐1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90‐μg test dose and a 720‐μg reference dose (42% cost reduction). Combining a 180‐μg test dose and a 720‐μg reference dose produced an estimated 36% cost reduction.

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Section: Methodsmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

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Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short‐Acting β‐Agonist Formulations

Zeng

Singh

Wang

et al. 2017

The Journal of Clinical Pharma

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“…21 32 33 52 71 There were no differences in the results of trials that used pressurised metered dose inhalers with and without spacer devices compared with alternative inhaler devices. However, this indirect subgroup comparison was not determined before the study and is therefore not a reliable method to assess the effectiveness of spacer devices.…”

Section: Resultsmentioning

confidence: 99%

Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering beta 2 agonists bronchodilators in asthma

Ram

Wright

Brocklebank

et al. 2001

BMJ

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Objectives To determine the clinical effectiveness of pressurised metered dose inhalers compared with other hand held inhaler devices for delivering short acting 2 agonists in stable asthma. Design Systematic review of randomised controlled trials. Data sources Cochrane Airways Group specialised trials database (which includes hand searching of 20 relevant journals), Medline, Embase, Cochrane controlled clinical trials register, pharmaceutical companies, and bibliographies of included trials. Trials All trials in children or adults with stable asthma that compared the pressurised metered dose inhaler (with or without a spacer device) against any other hand held inhaler device containing the same 2 agonist. Results 84 randomised controlled trials were included. No differences were found between the pressurised metered dose inhaler and any other hand held inhaler device for lung function, blood pressure, symptoms, bronchial hyperreactivity, systemic bioavailability, inhaled steroid requirement, serum potassium concentration, and use of additional relief bronchodilators. In adults, pulse rate was lower in those using the pressurised metered dose inhaler compared with those using Turbohaler (standardised mean difference 0.44, 95% confidence interval 0.05 to 0.84); patients preferred the pressurised metered dose inhaler to the Rotahaler (relative risk 0.53, 95% confidence interval 0.36 to 0.78); hydrofluoroalkane pressurised metered dose inhalers reduced the requirement for rescue short course oral steroids (relative risk 0.67, 0.49 to 0.91). Conclusions No evidence was found to show that alternative inhaler devices are more effective than standard pressurised metered dose inhalers for delivering acting 2 agonist bronchodilators in asthma. Pressurised metered dose inhalers remain the most cost effective delivery devices.

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“…No difference in methacholine challenge results following inhalation from a metered dose inhaler and when it is attached to a spacer have been reported [16]. In contrast, differences have been observed for salbutamol urinary excretion [17] and plasma drug concentrations [18] and also using gamma scintigraphy [19, 20].…”

Section: Discussionmentioning

confidence: 99%

Assessment of different methods of inhalation from salbutamol metered dose inhalers by urinary drug excretion and methacholine challenge

Tomlinson

Corlett

Allen

et al. 2005

Brit J Clinical Pharma

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AimsMethods to determine the lung delivery of inhaled bronchodilators from metered dose inhalers include urinary drug excretion 30 min post inhalation and methacholine challenge (P D 20 ). We have compared these two methods to differentiate lung delivery of salbutamol from metered dose inhalers using different inhalation methods. MethodsIn phase 1 of the study, on randomized study days, 12 mild asthmatics inhaled placebo, one and two 100 µ g salbutamol doses from a breath actuated metered dose inhaler, in randomized fashion on different days. In phase 2, they inhaled one 100 µ g salbutamol dose from a metered dose inhaler using a SLOW (20 l min − 1 ) and a FAST (60 l min − 1 ) inhalation technique and a slow inhalation delayed until after they had inhaled for 5 s (LATE). Urinary excretion of salbutamol (0-30 min) and P D 20 were measured after each dose. ResultsFollowing placebo, one and two 100 µ g salbutamol doses, the geometric mean for P D 20 was 0.10, 0.41 and 0.86 mg respectively and the mean (SD) urinary drug excretion after one and two doses was 2.25 (0.65) and 5.37 (1.36) µ g, respectively. After SLOW, FAST and LATE inhalations the geometric mean for P D 20 was 0.50, 0.40 and 0.42 mg, respectively, and mean (SD) salbutamol excretion was 2.67 (0.84), 1.90 (0.70) and 2.72 (0.67) µ g, respectively. Only the amount of drug excreted during the FAST compared with the SLOW and LATE inhalations showed a statistical difference (95% confidence interval on the difference 0.12, 1.54 and 0.06,1.59 µ g, respectively). ConclusionsUrinary salbutamol excretion but not P D 20 showed differences between the inhalation methods used. When using a metered dose inhaler slow inhalation is better and coordination is not essential if the patient is inhaling when they actuate a dose of the drug.

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The Protective Effect of Salbutamol Inhaled Using Different Devices on Methacholine Bronchoconstriction

Cited by 22 publications

References 24 publications

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short‐Acting β‐Agonist Formulations

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short‐Acting β‐Agonist Formulations

Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering beta 2 agonists bronchodilators in asthma

Assessment of different methods of inhalation from salbutamol metered dose inhalers by urinary drug excretion and methacholine challenge

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