Bioassay of salmeterol in children using methacholine challenge with impulse oscillometry

Pritish Mondal, Sandra Baumstein, Sreekala Prabhakaran, Mutasim Abu-Hasan, Yaohui Zeng, Sachinkumar Singh, Kai Wang, Richard C. Ahrens, Leslie Hendeles

Research output: Contribution to journalArticle

Abstract

Background Bronchoprovocation with methacholine (MC) is the most sensitive method of determining bioequivalence of inhaled bronchodilators. FEV1 is used to determine the endpoint, but many children cannot perform spirometry reproducibly. The purpose of this study was to determine whether MC, using impulse oscillometry (IOS) as the endpoint, can differentiate between two doses of salmeterol (SM). Methods This was a single-blind, randomized study of 10 subjects with mild stable asthma, ages 4-11 years. None were taking a long-acting β-agonist but most were on low-dose inhaled corticosteroid. On one study day, MC was performed 1 hr after one inhalation from each of two separate Advair 100/50 Diskus (100 μg salmeterol treatment). On a second day, MC was performed after one inhalation from Advair Diskus and one inhalation from Flovent Diskus 100 (50 μg salmeterol treatment). The provocative concentration of methacholine causing a 40% increase in total airway resistance (PC40R5) was calculated. Results The reduction in R5 (bronchodilator effect) was 15.5% and 18.4% for 50 and 100 μg, respectively (NS). After MC (bronchoprotective effect), the geometric mean (95%CI) PC40R5 (mg/ml) was 2.4 (1.3-4.4) during screening, 22.9 (8.5-61.6) after 50 μg SM and 47.0 (25.2-87.8) after 100 μg SM (P = 0.051 for 50 vs. 100 using a linear mixed effects model). No adverse effects were observed. Conclusions MC with IOS endpoint will be a useful method for determining bioequivalence of a generic inhaler in children. Seventy-two subjects will be required to achieve 80% power to assess bioequivalence of SM.

Original languageEnglish (US)
Pages (from-to)570-575
Number of pages6
JournalPediatric Pulmonology
Volume51
Issue number6
DOIs
StatePublished - Jun 1 2016

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Oscillometry
Methacholine Chloride
Biological Assay
Therapeutic Equivalency
Inhalation
Bronchodilator Agents
Single-Blind Method
Airway Resistance
Nebulizers and Vaporizers
Spirometry
Salmeterol Xinafoate
Adrenal Cortex Hormones
Asthma

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Cite this

Mondal, P., Baumstein, S., Prabhakaran, S., Abu-Hasan, M., Zeng, Y., Singh, S., ... Hendeles, L. (2016). Bioassay of salmeterol in children using methacholine challenge with impulse oscillometry. Pediatric Pulmonology, 51(6), 570-575. https://doi.org/10.1002/ppul.23345
Mondal, Pritish ; Baumstein, Sandra ; Prabhakaran, Sreekala ; Abu-Hasan, Mutasim ; Zeng, Yaohui ; Singh, Sachinkumar ; Wang, Kai ; Ahrens, Richard C. ; Hendeles, Leslie. / Bioassay of salmeterol in children using methacholine challenge with impulse oscillometry. In: Pediatric Pulmonology. 2016 ; Vol. 51, No. 6. pp. 570-575.
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abstract = "Background Bronchoprovocation with methacholine (MC) is the most sensitive method of determining bioequivalence of inhaled bronchodilators. FEV1 is used to determine the endpoint, but many children cannot perform spirometry reproducibly. The purpose of this study was to determine whether MC, using impulse oscillometry (IOS) as the endpoint, can differentiate between two doses of salmeterol (SM). Methods This was a single-blind, randomized study of 10 subjects with mild stable asthma, ages 4-11 years. None were taking a long-acting β-agonist but most were on low-dose inhaled corticosteroid. On one study day, MC was performed 1 hr after one inhalation from each of two separate Advair 100/50 Diskus (100 μg salmeterol treatment). On a second day, MC was performed after one inhalation from Advair Diskus and one inhalation from Flovent Diskus 100 (50 μg salmeterol treatment). The provocative concentration of methacholine causing a 40{\%} increase in total airway resistance (PC40R5) was calculated. Results The reduction in R5 (bronchodilator effect) was 15.5{\%} and 18.4{\%} for 50 and 100 μg, respectively (NS). After MC (bronchoprotective effect), the geometric mean (95{\%}CI) PC40R5 (mg/ml) was 2.4 (1.3-4.4) during screening, 22.9 (8.5-61.6) after 50 μg SM and 47.0 (25.2-87.8) after 100 μg SM (P = 0.051 for 50 vs. 100 using a linear mixed effects model). No adverse effects were observed. Conclusions MC with IOS endpoint will be a useful method for determining bioequivalence of a generic inhaler in children. Seventy-two subjects will be required to achieve 80{\%} power to assess bioequivalence of SM.",
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Mondal, P, Baumstein, S, Prabhakaran, S, Abu-Hasan, M, Zeng, Y, Singh, S, Wang, K, Ahrens, RC & Hendeles, L 2016, 'Bioassay of salmeterol in children using methacholine challenge with impulse oscillometry', Pediatric Pulmonology, vol. 51, no. 6, pp. 570-575. https://doi.org/10.1002/ppul.23345

Bioassay of salmeterol in children using methacholine challenge with impulse oscillometry. / Mondal, Pritish; Baumstein, Sandra; Prabhakaran, Sreekala; Abu-Hasan, Mutasim; Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai; Ahrens, Richard C.; Hendeles, Leslie.

In: Pediatric Pulmonology, Vol. 51, No. 6, 01.06.2016, p. 570-575.

Research output: Contribution to journalArticle

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T1 - Bioassay of salmeterol in children using methacholine challenge with impulse oscillometry

AU - Mondal, Pritish

AU - Baumstein, Sandra

AU - Prabhakaran, Sreekala

AU - Abu-Hasan, Mutasim

AU - Zeng, Yaohui

AU - Singh, Sachinkumar

AU - Wang, Kai

AU - Ahrens, Richard C.

AU - Hendeles, Leslie

PY - 2016/6/1

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N2 - Background Bronchoprovocation with methacholine (MC) is the most sensitive method of determining bioequivalence of inhaled bronchodilators. FEV1 is used to determine the endpoint, but many children cannot perform spirometry reproducibly. The purpose of this study was to determine whether MC, using impulse oscillometry (IOS) as the endpoint, can differentiate between two doses of salmeterol (SM). Methods This was a single-blind, randomized study of 10 subjects with mild stable asthma, ages 4-11 years. None were taking a long-acting β-agonist but most were on low-dose inhaled corticosteroid. On one study day, MC was performed 1 hr after one inhalation from each of two separate Advair 100/50 Diskus (100 μg salmeterol treatment). On a second day, MC was performed after one inhalation from Advair Diskus and one inhalation from Flovent Diskus 100 (50 μg salmeterol treatment). The provocative concentration of methacholine causing a 40% increase in total airway resistance (PC40R5) was calculated. Results The reduction in R5 (bronchodilator effect) was 15.5% and 18.4% for 50 and 100 μg, respectively (NS). After MC (bronchoprotective effect), the geometric mean (95%CI) PC40R5 (mg/ml) was 2.4 (1.3-4.4) during screening, 22.9 (8.5-61.6) after 50 μg SM and 47.0 (25.2-87.8) after 100 μg SM (P = 0.051 for 50 vs. 100 using a linear mixed effects model). No adverse effects were observed. Conclusions MC with IOS endpoint will be a useful method for determining bioequivalence of a generic inhaler in children. Seventy-two subjects will be required to achieve 80% power to assess bioequivalence of SM.

AB - Background Bronchoprovocation with methacholine (MC) is the most sensitive method of determining bioequivalence of inhaled bronchodilators. FEV1 is used to determine the endpoint, but many children cannot perform spirometry reproducibly. The purpose of this study was to determine whether MC, using impulse oscillometry (IOS) as the endpoint, can differentiate between two doses of salmeterol (SM). Methods This was a single-blind, randomized study of 10 subjects with mild stable asthma, ages 4-11 years. None were taking a long-acting β-agonist but most were on low-dose inhaled corticosteroid. On one study day, MC was performed 1 hr after one inhalation from each of two separate Advair 100/50 Diskus (100 μg salmeterol treatment). On a second day, MC was performed after one inhalation from Advair Diskus and one inhalation from Flovent Diskus 100 (50 μg salmeterol treatment). The provocative concentration of methacholine causing a 40% increase in total airway resistance (PC40R5) was calculated. Results The reduction in R5 (bronchodilator effect) was 15.5% and 18.4% for 50 and 100 μg, respectively (NS). After MC (bronchoprotective effect), the geometric mean (95%CI) PC40R5 (mg/ml) was 2.4 (1.3-4.4) during screening, 22.9 (8.5-61.6) after 50 μg SM and 47.0 (25.2-87.8) after 100 μg SM (P = 0.051 for 50 vs. 100 using a linear mixed effects model). No adverse effects were observed. Conclusions MC with IOS endpoint will be a useful method for determining bioequivalence of a generic inhaler in children. Seventy-two subjects will be required to achieve 80% power to assess bioequivalence of SM.

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