Evaluation of potential for pharmacokinetic interaction between mometasone furoate and formoterol fumarate after oral inhalation from a fixed-dose combination metered-dose inhaler device.

Abstract

A fixed-dose combination (FDC) containing mometasone furoate (MF) and formoterol fumarate (F) in a pressurized metered dose inhaler (MDI) is approved for asthma and is being developed for COPD. This randomized, open-label, 4-period crossover study compared single-dose pharmacokinetics of MF 800 µg; F 20 µg; MF 800 µg + F 20 µg coadministered (MF + F); and MF 800 µg/F 20 µg (MF/F) FDC in healthy subjects. MF, F, and MF + F were administered from single-ingredient MDI devices. MF and formoterol plasma samples were obtained predose and up to 48 hours post dose for estimation of AUC0-tf (primary endpoint) and Cmax . Treatments were deemed comparable if the 90% CIs for the geometric mean ratios (GMRs) fell within 70-143%. MF AUC0-tf was comparable following treatment with MF + F versus MF (GMR 98%; 90% CI 85-113%) and MF/F versus MF + F (GMR 95%; 90% CI 82-109%). Similarly, formoterol AUC0-tf was comparable following treatment with MF + F versus F (GMR 98%; 90% CI 77-124%) and MF/F versus MF + F (GMR 108%; 90% CI 85-136%). The 90% CIs for MF and formoterol Cmax fell within the prespecified comparability bounds for all comparisons. Systemic exposures to MF and formoterol were similar following treatment with the FDC MDI device versus individual or concomitant use of single-ingredient MDI devices.