Lung Delivery of Indacaterol and Mometasone Furoate Following Inhalation of QMF149 in Healthy Volunteers.
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.
Drug Metabolism and Pharmacokinetics, Clinical Pharmacokinetics/Pharmacodynamics, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
Soniya S
SS
Vaidya
Translational Medicine, Novartis Institutes for BioMedical Research, Horsham, West Sussex, UK.
Sanjeev
S
Khindri
Translational Medicine, Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
Suzanne
S
Maahs
Integrated Information and Sciences, Novartis Healthcare Pvt Ltd, Hyderabad, India.
Surendra
S
Machineni
Drug Metabolism and Pharmacokinetics, Advanced BA & Automation, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Hisanori
H
Hara
Seaview Research, Inc, Miami, FL, USA.
Axel
A
Juan
Drug Metabolism and Pharmacokinetics, Clinical Pharmacokinetics/Pharmacodynamics, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Günther
G
Kaiser
D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002606:Charcoal / Q000737:chemistry; D018592:Cross-Over Studies; D004338:Drug Combinations; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D009330:Nebulizers and Vaporizers; D011244:Pregnadienediols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014018:Tissue Distribution; D055815:Young Adult
D058666:Adrenergic beta-2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D007189:Indans; D011244:Pregnadienediols; C000600413:QMF149; D015363:Quinolones; D002606:Charcoal
QMF149; indacaterol; lung delivery; mometasone furoate; pharmacokinetics