title: 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.
abstract: 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).
  
  
  
  Healthy, non-smoking adults, 18-65 years with body mass index 18-29 kg/m(2) (N = 12) received MF 800 µg/F 20 µg via MF/F-MDI or MF 800 µg via MF-DPI twice daily for 5 days separated by a 7-day period. MF pharmacokinetics (AUC(0-12 hour) , Cmax , and Tmax ) were measured at Day 1 and 5 after each treatment. Safety and tolerability were assessed.
  
  
  
  Systemic exposure to MF based on AUC(0-12 hour) was ∼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 Cmax 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.
  
  
  
  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.
authors.affiliation: Clinical Pharmacology, Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors.forename: Teddy
authors.initials: T
authors.lastname: Kosoglou
authors.affiliation: Exploratory Drug Metabolism, Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors.forename: James
authors.initials: J
authors.lastname: Hubbell
authors.affiliation: Bio/Toxicokinetics, Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Kantesaria
authors.affiliation: Global Scientific and Medical Publications, Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Hanson
authors.affiliation: Clinical Pharmacology, Merck & Co., Inc., Whitehouse Station, NJ, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Cutler
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D058995:Dry Powder Inhalers; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D036501:Metered Dose Inhalers; D008875:Middle Aged; D000068758:Mometasone Furoate, Formoterol Fumarate Drug Combination / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D009426:Netherlands; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D000068758:Mometasone Furoate, Formoterol Fumarate Drug Combination
keywords: bioavailability; dry-powder inhaler; formoterol fumarate; metered-dose inhaler; mometasone furoate; systemic exposure