title: Bioassay of salmeterol in children using methacholine challenge with impulse oscillometry.
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 (PC40 R5 ) 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) PC40 R5 (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. Pediatr Pulmonol. 2016;51:570-575. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Pediatrics, College of Medicine, Penn State University, State College, Pennsylvania.
authors.forename: Pritish
authors.initials: P
authors.lastname: Mondal
authors.affiliation: Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida.
authors.forename: Sandra
authors.initials: S
authors.lastname: Baumstein
authors.affiliation: Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Sreekala
authors.initials: S
authors.lastname: Prabhakaran
authors.affiliation: Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida.
authors.forename: Mutasim
authors.initials: M
authors.lastname: Abu-Hasan
authors.affiliation: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Sachinkumar
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Ahrens
authors.affiliation: Department of Pharmacotherapy and Translational Research, College of Pharmacy and Department of Pediatrics, University of Florida, Gainesville, FL.
authors.forename: Leslie
authors.initials: L
authors.lastname: Hendeles
mesh_terms: D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D001681:Biological Assay / Q000379:methods*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage* / Q000009:adverse effects*; D009991:Oscillometry; D011446:Prospective Studies; D000068299:Salmeterol Xinafoate / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016037:Single-Blind Method; D013810:Therapeutic Equivalency
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D000068299:Salmeterol Xinafoate
keywords: bioequivalence; bronchoprovocation; inhaled therapy; β-agonists