title: Comparison of the systemic bioavailability of mometasone furoate after oral inhalation from a mometasone furoate/formoterol fumarate metered-dose inhaler versus a mometasone furoate dry-powder inhaler in patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Coadministration of mometasone furoate (MF) and formoterol fumarate (F) produces additive effects for improving symptoms and lung function and reduces exacerbations in patients with asthma and chronic obstructive pulmonary disease (COPD). The present study assessed the relative systemic exposure to MF and characterized the pharmacokinetics of MF and formoterol in patients with COPD.
  
  
  METHODS
  This was a single-center, randomized, open-label, multiple-dose, three-period, three-treatment crossover study. The following three treatments were self-administered by patients (n = 14) with moderate-to-severe COPD: MF 400 μg/F 10 μg via a metered-dose inhaler (MF/F MDI; DULERA(®)/ZENHALE(®)) without a spacer device, MF/F MDI with a spacer, or MF 400 μg via a dry-powder inhaler (DPI; ASMANEX(®) TWISTHALER(®)) twice daily for 5 days. Plasma samples for MF and formoterol assay were obtained predose and at prespecified time points after the last (morning) dose on day 5 of each period of the crossover. The geometric mean ratio (GMR) as a percent and the corresponding 90% confidence intervals (CI) were calculated for treatment comparisons.
  
  
  RESULTS
  Systemic MF exposure was lower (GMR 77%; 90% CI 58, 102) following administration by MF/F MDI compared to MF DPI. Additionally, least squares geometric mean systemic exposures of MF and formoterol were lower (GMR 72%; 90% CI 61, 84) and (GMR 62%; 90% CI 52, 74), respectively, following administration by MF/F MDI in conjunction with a spacer compared to MF/F MDI without a spacer. MF/F MDI had a similar adverse experience profile as that seen with MF DPI. All adverse experiences were either mild or moderate in severity; no serious adverse experience was reported.
  
  
  CONCLUSIONS
  Systemic MF exposures were lower following administration by MF/F MDI compared with MF DPI. Additionally, systemic MF and formoterol exposures were lower following administration by MF/F MDI with a spacer versus without a spacer. The magnitude of these differences with respect to systemic exposure was not clinically relevant.
authors.affiliation: Clinical Pharmacology, Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USA. teddy.kosoglou2@merck.com
authors.forename: Teddy
authors.initials: T
authors.lastname: Kosoglou
authors.forename: James
authors.initials: J
authors.lastname: Hubbell
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Xuan
authors.forename: David L
authors.initials: DL
authors.lastname: Cutler
authors.forename: Alan G
authors.initials: AG
authors.lastname: Meehan
authors.forename: Bhavna
authors.initials: B
authors.lastname: Kantesaria
authors.forename: Bret A
authors.initials: BA
authors.lastname: Wittmer
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004338:Drug Combinations; D058995:Dry Powder Inhalers; D004983:Ethanolamines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D000068656:Mometasone Furoate; D011244:Pregnadienediols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D000068759:Formoterol Fumarate
keywords: chronic obstructive pulmonary disease; dry-powder inhaler; metered-dose inhaler; mometasone furoate; pharmacokinetics; systemic exposure