An evaluation of the systemic bioavailability of mometasone furoate (MF) after oral inhalation from a MF/formoterol fumarate metered‐dose inhaler versus an MF dry‐powder inhaler in healthy subjects

Purpose: This randomized, open-label, multiple-dose, two-period, crossover study compared the systemic bioavailability of mometasone furoate (MF) administered from a metered-dose inhaler containing MF and formoterol fumarate (F) (MF/F-MDI) versus MF administered from a single-ingredient dry-powder inhaler (MF-DPI). Methods: Healthy, non-smoking adults, 18-65 years with body mass index 18-29 kg/m(2) (N = 12) received MF 800 mu g/F 20 mu g via MF/F-MDI or MF 800 mu g via MF-DPI twice daily for 5 days separated by a 7-day period. MF pharmacokinetics (AUC((0-12 hour)), C-max, and T-max) were measured at Day 1 and 5 after each treatment. Safety and tolerability were assessed. Results: Systemic exposure to MF based on AUC((0-12 hour)) was similar to 25% lower following MDI versus DPI administration. The Day 5 geometric mean ratio (MDI/DPI) estimates (90% confidence intervals [CI]) for AUC((0-12 hour)) and C-max were 0.747 (0.61, 0.91) and 0.606 (0.49, 0.75), respectively. The accumulation index (R) value for MF was higher following MDI (3.81-fold) versus DPI administration (2.34-fold) indicative of prolonged absorption. The most common adverse events were tremor, headache, and catheter site pain. Conclusions: Systemic exposure to MF was lower following multiple-dose MF/F-MDI administration versus MF-DPI administration. The magnitude of this difference is not considered to be clinically important. MF/F-MDI was safe and generally well tolerated.