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Pharmacokinetics and pharmacodynamics of GSK961081, a novel inhaled muscarinic antagonist β 2 ‐agonist, and fluticasone propionate administered alone, concurrently and as a combination blend formulation in healthy volunteers
Author(s) -
Norris Virginia,
Ambery Claire,
Riley Trevor
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.105
Subject(s) - fluticasone propionate , medicine , pharmacokinetics , pharmacodynamics , pharmacology , crossover study , fluticasone , antagonist , muscarinic antagonist , anesthesia , corticosteroid , receptor , alternative medicine , pathology , placebo
Objective To investigate the pharmacokinetics and pharmacodynamics of inhaled GSK961081 and fluticasone propionate (FP) given alone, concurrently and as a combination blend formulation. Methods The study was double‐blind, double‐dummy, four‐way crossover. Twenty‐four healthy volunteers took single doses of the following in randomized order: (1) GSK961081 800 µg; (2) FP 500 µg; (3) GSK961081 800 µg and FP 500 µg as a blend formulation; and (4) GSK961081 800 µg and FP 500 µg concurrently via separate inhalers. The eLung breathing simulator was also used for the in vitro characterization of the formulations. Results There was no pharmacokinetic interaction when GSK961081 and FP were administered concurrently. Mean C max and AUC (0−t) of GSK961081 were lower (∼20%) and mean C max and AUC (0−t) of FP were higher (two fold) following GSK961081/FP blend formulation compared to concurrent or the individual components alone. There was an increase in the FP in vitro ex‐throat dose for the GSK961081/FP blend from the eLung breathing simulator. Serum cortisol suppression was greater with GSK961081/FP blend, with lower (∼10%) cortisol levels than after GSK961081 + FP concurrent or FP alone. Conclusion GSK961081/FP blend formulation was associated with an increase in FP systemic exposure and greater serum cortisol suppression.