title: Single-dose pharmacokinetics and safety pharmacodynamics of formoterol delivered by two different dry powder inhalers.
abstract: The present study aimed at assessing the pharmacokinetics (PK) and safety pharmacodynamics (PD) of 24 microg formoterol delivered via a Novolizer and via an Aerolizer in healthy subjects. This was a randomized, open-label, crossover study. Beside PK, serum potassium, and glucose profiles, vital signs, and ECG were recorded. Twenty-nine subjects (15 males) were enrolled. The inhalation maneuver had to be repeated by 19 subjects using the Aerolizer and 1 subject using a Novolizer. While eight (28%) subjects completely failed to inhale correctly via the Aerolizer (four were identified by the investigators immediately after inhalation, another four by bioanalytics later), all did it correctly via the Novolizer. The bioanalytical evaluation indicated two distinct serum peaks. The shapes of serum concentration-time profiles were more homogeneous after inhaling via the Novolizer than via the Aerolizer. After adjusting for the delivered dose the Cmax of formoterol predicting pulmonary absorption was higher after the Novolizer than after the Aerolizer, while the average AUC0-infinity levels indicating total systemic exposure were equivalent. There was no evidence for different pharmacodynamic behavior with respect to serum potassium and glucose profiles, vital signs, and ECG. The Novolizer yields higher pulmonary absorption of formoterol than the Aerolizer and equivalent safety profiles. Considering the lower variability of PK profiles and the higher proportion of correct inhalations, formoterol is more reliably inhaled via Novolizer.
authors.affiliation: MEDA Pharma GmbH & Co. KG, Bad Homburg, Germany. ursula.petzold@medapharma.de
authors.forename: Ursula
authors.initials: U
authors.lastname: Petzold
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Kremer
authors.forename: Duc Tung
authors.initials: DT
authors.lastname: Nguyen
authors.forename: Ullrich
authors.initials: U
authors.lastname: Munzel
authors.forename: Hartmut
authors.initials: H
authors.lastname: Dietrich
authors.forename: Joachim
authors.initials: J
authors.lastname: Maus
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011208:Powders; D055815:Young Adult
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D011208:Powders; D000068759:Formoterol Fumarate