Lung Delivery of Indacaterol and Mometasone Furoate Following Inhalation of QMF149 in Healthy Volunteers

• Published in: Clinical pharmacology in drug development Vol. 5; no. 4; pp. 285 - 295
• Main Authors: Vaidya, Soniya S., Khindri, Sanjeev, Maahs, Suzanne, Machineni, Surendra, Hara, Hisanori, Juan, Axel, Kaiser, Günther
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2016; Wiley Subscription Services, Inc
• Subjects: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists - administration & dosage; Adrenergic beta-2 Receptor Agonists - adverse effects; Adrenergic beta-2 Receptor Agonists - pharmacokinetics; Adult; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Anti-Inflammatory Agents - pharmacokinetics; Area Under Curve; Biological Availability; Charcoal - chemistry; Cross-Over Studies; Drug Combinations; Drug Delivery Systems; Female; Humans; indacaterol; Indans - administration & dosage; Indans - adverse effects; Indans - pharmacokinetics; Lung - metabolism; lung delivery; Male; mometasone furoate; Nebulizers and Vaporizers; pharmacokinetics; Pregnadienediols - administration & dosage; Pregnadienediols - adverse effects; Pregnadienediols - pharmacokinetics; QMF149; Quinolones - administration & dosage; Quinolones - adverse effects; Quinolones - pharmacokinetics; Tissue Distribution; Young Adult; pharmacokinetics; lung delivery; QMF149; indacaterol; mometasone furoate
• ISSN: 2160-763X; 2160-7648; 2160-7648
• DOI: 10.1002/cpdd.245

This single‐dose, 4‐period crossover study evaluated the pharmacokinetics (PK) of the β2‐agonist indacaterol maleate and the corticosteroid mometasone furoate (MF) after inhalation of a fixed‐dose combination (QMF149, indacaterol maleate/MF, 500/400 μg) via the Twisthaler (TH) device with and without activated charcoal and postdose mouth rinsing in healthy volunteers. The PK of indacaterol maleate 300 μg inhaled via the Breezhaler (BRZ) device was also characterized. Relative bioavailability of indacaterol and MF for inhalation with versus without charcoal, based on AUClast, was 0.25 (90% confidence interval [CI], 0.18–0.35) and 0.70 (90%CI, 0.52–0.93), respectively. Thus, 25% and 70% of systemic exposure of indacaterol and MF, respectively was due to pulmonary absorption and 75% and 30%, respectively, was due to gastrointestinal absorption. Mouth rinsing reduced the systemic exposure of indacaterol by approximately 35% but had no relevant effect on the exposure of MF. Dose‐normalized AUClast for indacaterol inhaled via the BRZ device was 2.3‐fold higher than QMF149 via the TH device. All treatments had a good safety profile and were well tolerated. Data from this study and comparison with inhalation of indacaterol via the BRZ device suggest that the latter was more efficient than the TH device regarding lung delivery of indacaterol.