title: Pharmacokinetics, Safety, and Tolerability of Once-Daily Intranasal Fluticasone Furoate and Levocabastine Administered Alone or Simultaneously as fluticasone Furoate/Levocabastine Fixed-Dose Combination.
abstract: OBJECTIVE
  The purpose of this study was to investigate potential systemic pharmacokinetic interactions between intranasal fluticasone furoate (FF) and levocabastine (LEVO) when delivered simultaneously via a metered atomizing spray pump.
  
  
  METHODS
  This was a randomized, open-label, crossover study. Healthy male and female subjects (n = 30) received once-daily repeat doses of FF/LEVO (100/200 μg) as a fixed-dose combination (FDC), FF (110 μg), or LEVO (200 μg) for 7 days. FF and LEVO plasma pharmacokinetics (0-24 hours) were measured on day 7, with safety assessments over the study duration.
  
  
  RESULTS
  Systemic exposure to LEVO was similar when administered as FF/LEVO FDC or LEVO alone. Following FF/LEVO FDC or FF alone, the majority (>99%) of FF concentrations were nonquantifiable, that is, below the lower limit of quantification of 10 pg/mL. All treatments were well tolerated, and adverse event incidence was similar across the treatment groups.
  
  
  CONCLUSIONS
  These results suggest that in healthy subjects, for LEVO, there is no pharmacokinetic interaction with FF when delivered as FF/LEVO FDC. As the majority of data were below the assay sensitivity for FF, any potential differences in the bioavailability of FF when delivered alone or as FF/LEVO FDC could not be established. There was no clinically relevant impact on safety/tolerability when FF/LEVO was coadministered.
authors.affiliation: GSK R&D, Gunnels Wood Road, Stevenage and Ware, Herts, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Allen
authors.affiliation: GSK R&D, Gunnels Wood Road, Stevenage and Ware, Herts, UK.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Murdoch
authors.affiliation: GSK R&D, Gunnels Wood Road, Stevenage and Ware, Herts, UK.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bareille
authors.affiliation: GSK R&D, Abbotsford, Australia.
authors.forename: Olivia
authors.initials: O
authors.lastname: Burns
authors.affiliation: GSK R&D, Gunnels Wood Road, Stevenage and Ware, Herts, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hughes
authors.affiliation: GSK R&D, Bangalore, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Gupta
authors.affiliation: GSK R&D, Gunnels Wood Road, Stevenage and Ware, Herts, UK.
authors.forename: Sam R
authors.initials: SR
authors.lastname: Miller
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001682:Biological Availability; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000730:Androstadienes; D004338:Drug Combinations; D005938:Glucocorticoids; D039563:Histamine H1 Antagonists, Non-Sedating; D010880:Piperidines; C047340:levocabastine; C523187:fluticasone furoate
keywords: combination therapy; fluticasone furoate; intranasal; levocabastine; pharmacokinetics