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The pharmacodynamics, pharmacokinetics, safety and tolerability of inhaled fluticasone furoate and vilanterol administered alone or simultaneously as fluticasone furoate/vilanterol
Author(s) -
Kempsford Rodger,
Allen Ann,
Bareille Philippe,
Hamilton Melanie,
Cheesbrough Anne
Publication year - 2014
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.160
Subject(s) - medicine , fluticasone propionate , dry powder inhaler , pharmacodynamics , pharmacokinetics , tolerability , crossover study , placebo , bioequivalence , pharmacology , inhalation , anesthesia , inhaler , adverse effect , asthma , alternative medicine , pathology
Purpose To investigate the potential for systemic pharmacokinetic (PK) and pharmacodynamic (PD) interactions between inhaled fluticasone furoate (FF) and vilanterol (VI) when delivered simultaneously via the ELLIPTA™ dry powder inhaler (DPI). Methods Randomized, double‐blind, placebo‐controlled, crossover study. Healthy subjects (n = 16) received single doses of FF (800 mcg), VI (100 mcg), FF/VI (800/100 mcg), and placebo. Endpoints measured were systemic PD (FF: serum cortisol; VI: heart rate), FF and VI plasma PK (0–48 hours), pharyngometry, inhalation and breath hold profiles and safety assessments. Results Treatment differences [90% confidence interval (CI)] in weighted mean serum cortisol (0–24 hours) were 12.3% [4.4, 20.9] (FF/VI vs. FF) and for maximum heart rate (0–4 hours) were −1.2 bpm [−4.6, 2.1] (FF/VI vs. VI). When delivered simultaneously, FF and VI systemic exposures were slightly lower (<20%) versus delivery of either agent alone (although this was not a formal bioequivalence study). In vitro simulation of selected inhalation profiles and modeling supported the PK and PD findings. FF/VI, FF and VI were well tolerated with an AE incidence comparable to placebo. Conclusions These results suggest there was a slight PK interaction and no PD interactions of concern between inhaled FF and VI when delivered simultaneously via the ELLIPTA DPI in healthy subjects.