title: Pharmacokinetics of fluticasone propionate and salmeterol delivered as a combination dry powder via a capsule-based inhaler and a multi-dose inhaler.
abstract: OBJECTIVE
  To compare salmeterol (SALM) and fluticasone propionate (FP) systemic exposure following inhaled salmeterol/fluticasone propionate combination (SFC) from a unit-dose capsule-based inhaler (Rotacaps(®)/Rotahaler(®)) and a multi-dose dry powder inhaler (Diskus(®)) in healthy volunteers.
  
  
  METHODS
  An open-label, randomised, repeat-dose, cross-over, adaptive design study (n = 36 in each part) evaluated SFC 50/250 μg and SFC 50/100 μg in Rotacaps used with two types of Rotahaler inhalers (airflow resistance similar to (S) and lower than (L) Diskus) versus the Diskus. Primary endpoints were area under the concentration-time curve over the dosing interval [AUC0-τ] and maximum plasma concentration [Cmax].
  
  
  RESULTS
  SFC 50/250 μg Rotacaps/Rotahaler (S) showed 1.2-1.9-fold greater FP and SALM systemic exposure compared with Diskus. FP and SALM systemic exposure were comparable to DISKUS following SFC 50/250 μg Rotacaps/Rotahaler (L) (90% CI of ratio of Rotahaler to DISKUS within 0.8-1.25) for salmeterol (AUC0-τ and Cmax) and FP (AUC0-τ). Following SFC 50/100 μg Rotacaps/Rotahaler (L), FP and SALM systemic exposures were 1.2-1.4 fold higher in terms of FP (AUC0-τ and Cmax) and salmeterol (Cmax) compared with Diskus. SFC at both doses and via both inhalers was well tolerated.
  
  
  CONCLUSIONS
  SFC 50/250 μg Rotacaps/Rotahaler (L) showed comparable systemic exposure to Diskus in terms of FP AUC and SALM AUC and Cmax. These results merit further progression of SFC 50/250 μg Rotacaps/Rotahaler (L) to phase 3 clinical evaluation in asthma and COPD patients. The lack of pharmacokinetic comparability between the inhalers for SFC 50/100 μg requires further evaluation.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA. Electronic address: rashmi.s.mehta@gsk.com.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Mehta
authors.affiliation: GlaxoSmithKline, Stockley Park, Uxbridge, UK.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Daley-Yates
authors.affiliation: GlaxoSmithKline, Stockley Park, Uxbridge, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Jenkins
authors.affiliation: GlaxoSmithKline, Melbourne, Victoria, Australia.
authors.forename: Joseph
authors.initials: J
authors.lastname: Bianco
authors.affiliation: GlaxoSmithKline, Stevenage, UK.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Stylianou
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Margaret D
authors.initials: MD
authors.lastname: Louey
authors.affiliation: GlaxoSmithKline, Stockley Park, Uxbridge, UK.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Chan
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D058995:Dry Powder Inhalers; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D013566:Sympathomimetics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids; D013566:Sympathomimetics
keywords: Diskus; Dry powder inhaler; Fluticasone propionate; Rotacaps; Rotahaler; Salmeterol