Pharmacokinetics and pharmacodynamics of GSK961081, a novel inhaled muscarinic antagonist β₂‐agonist, and fluticasone propionate administered alone, concurrently and as a combination blend formulation in healthy volunteers

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 Cmax and AUC(0-t) of GSK961081 were lower (∼20%) and mean Cmax 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.