title: Tiotropium Respimat(®) Versus HandiHaler(®): Comparison of Bronchodilator Efficacy of Various Doses in Clinical Trials.
abstract: The long-acting muscarinic antagonist tiotropium bromide is approved in many countries as maintenance therapy for chronic obstructive pulmonary disease (COPD). Tiotropium is available as a dry-powder formulation delivered via HandiHaler(®) (18 μg once daily) and is now also approved as an aqueous solution delivered via the Respimat(®) Soft Mist™ Inhaler (5 μg once daily, 2 puffs of 2.5 µg). Several studies have compared the efficacy of tiotropium HandiHaler (18 μg once daily) with different doses of Respimat. We aimed to compare available bronchodilator efficacy data of once-daily Respimat 1.25, 2.5, 5, 10, 20 µg, and HandiHaler 18 µg to investigate which dose of tiotropium delivered by Respimat is the closest match to tiotropium HandiHaler.
  
  
  
  Evaluation of six clinical trials (duration from 3 weeks to 2-3 years) that included lung function measures (trough forced expiratory volume in 1 s and trough forced vital capacity) as key outcomes.
  
  
  
  In the six trials, bronchodilator efficacy of Respimat 5 μg and HandiHaler 18 μg was similar; however, reduced bronchodilator efficacy was observed with lower doses of Respimat (1.25 and 2.5 μg).
  
  
  
  These findings support the use of the marketed once-daily dose of Respimat 5 μg for the maintenance treatment of patients with COPD.
  
  
  
  Boehringer Ingelheim.
authors.affiliation: Pulmonary and Rehabilitation Medicine, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK. pmacal@liverpool.ac.uk.
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
authors.affiliation: Clinical Development + Medical Affairs, Boehringer Ingelheim, Ingelheim, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Könen-Bergmann
authors.affiliation: Medicine TA Respiratory Diseases, Boehringer Ingelheim, Ingelheim, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Richard
authors.affiliation: Statistics, Boehringer Ingelheim, Bracknell, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Bell
authors.affiliation: Clinical Airway Research, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.
authors.forename: Jens M
authors.initials: JM
authors.lastname: Hohlfeld
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D000069447:Tiotropium Bromide
keywords: Bronchodilator; Chronic obstructive pulmonary disease (COPD); Dose–response; Efficacy; Long-acting muscarinic antagonist; Lung function; Once-daily; Pulmonology; Respimat®; Spirometry; Tiotropium