title: Systemic Exposures of Fluticasone Propionate and Salmeterol Following Inhalation via Metered Dose Inhaler with the Mini Spacer Compared with the Aerochamber Plus Spacer.
abstract: The Mini Spacer has been developed for use with Ventolin(®) metered dose inhalers (MDIs) to improve accessibility to affordable spacers in developing countries. To ensure patient safety is not compromised if the Mini Spacer is used off-label with fluticasone propionate (FP) or salmeterol/FP combination (SFC) MDIs (currently not recommended), this study compared the systemic exposure of FP and salmeterol following delivery of FP and SFC MDIs with the Mini Spacer and the Aerochamber Plus(®) spacer (Aerochamber).
  
  
  
  This was an open-label, randomized, single dose, crossover study in healthy subjects that evaluated four treatments: i) FP 250 μg MDI with Mini Spacer; ii) FP 250 μg MDI with Aerochamber; iii) SFC 25/250 μg with Mini Spacer; iv) SFC 25/250 μg with Aerochamber. There was a minimum 7 day washout between treatments. Pharmacokinetic samples were collected over 24 hours post-dose. The co-primary endpoints were FP area under the concentration-time curve from time zero to 24 h [FP AUC(0-24)] and salmeterol maximum plasma concentration [Cmax].
  
  
  
  FP systemic exposure in terms of AUC(0-24) was lower following inhalation with the Mini Spacer compared with the Aerochamber for both FP 250 μg (Mini Spacer/Aerochamber Ratio 0.76 [90% CI: 0.57-1.01]) and SFC 25/250 μg (Ratio 0.74 [90% CI: 0.56-0.99]). Salmeterol systemic exposure was also lower following SFC 25/250 μg with Mini Spacer compared with Aerochamber (Cmax Ratio 0.90 [90% CI 0.48-1.66]). The incidence of adverse events was low and similar with each treatment.
  
  
  
  In the event of use of the Mini Spacer with FP and SFC MDIs, which is not recommended, FP and salmeterol systemic exposure is unlikely to be higher than if MDIs were to be used with the Aerochamber. However, these data do not indicate that the Mini Spacer and Aerochamber are interchangeable.
authors.affiliation: 1 GlaxoSmithKline, Research Triangle Park , North Carolina, United States .
authors.forename: Rashmi
authors.initials: R
authors.lastname: Mehta
authors.affiliation: 2 GlaxoSmithKline , Stockley Park, Uxbridge, United Kingdom .
authors.forename: Mickael
authors.initials: M
authors.lastname: Montembault
authors.affiliation: 2 GlaxoSmithKline , Stockley Park, Uxbridge, United Kingdom .
authors.forename: Francis
authors.initials: F
authors.lastname: Warren
authors.affiliation: 3 Quantitative Sciences India , GlaxoSmithKline, Bangalore, India .
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Gupta
authors.affiliation: 2 GlaxoSmithKline , Stockley Park, Uxbridge, United Kingdom .
authors.forename: Noushin
authors.initials: N
authors.lastname: Brealey
authors.affiliation: 2 GlaxoSmithKline , Stockley Park, Uxbridge, United Kingdom .
authors.forename: Alison
authors.initials: A
authors.lastname: Moore
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D036503:Inhalation Spacers; D008131:London; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids
keywords: fluticasone propionate; healthy volunteers; metered dose inhaler; salmeterol; systemic exposure