24-hour bronchodilation following a single dose of the novel β(2)-agonist olodaterol in COPD

Pulm Pharmacol Ther. 2011 Dec;24(6):666-72. doi: 10.1016/j.pupt.2011.07.006. Epub 2011 Aug 6.


Background: Current guidelines recommend long-acting bronchodilators as maintenance therapy in COPD when symptoms are not adequately controlled with short-acting agents. Olodaterol is a novel long-acting β(2)-adrenoceptor agonist with a pre-clinical profile that suggests 24-h bronchodilation may be achieved with once-daily administration.

Objective: To assess dose- and time-response in terms of bronchodilator efficacy, and to evaluate pharmacokinetics, safety and tolerability of single doses of olodaterol administered via Respimat(®) Soft Mist™ Inhaler in COPD patients.

Methods: A single-center, double-blind, placebo-controlled, 5-way crossover study including 24-h spirometry (FEV(1), FVC), safety, tolerability and pharmacokinetics (in a subset of patients) following dosing of olodaterol 2 μg, 5 μg, 10 μg and 20 μg; the washout period between test-days was at least 14 days. Primary endpoint of the study was the 24-h post-dosing FEV(1). Patients participating in the pharmacokinetic assessments continued in an open-label extension phase to establish pharmacokinetics of olodaterol 40 μg.

Results: 36 patients were assigned to treatment; mean baseline prebronchodilator FEV(1) was 1.01 L (37% predicted normal). All doses of olodaterol provided significantly greater bronchodilation compared to placebo in 24-h FEV(1) post-dose (p < 0.001); a clear dose-response relationship was observed, with values ranging from 0.070 L for olodaterol 2 μg to 0.119 L for olodaterol 20 μg. Similarly, olodaterol was superior to placebo (p < 0.001) in peak FEV(1) (0.121 L to 0.213 L) and average FEV(1) both during the daytime (0-12 h; ranging from 0.099 L to 0.184 L) and night-time (12-24 h; ranging from 0.074 L to 0.141 L). FVC results were consistent with those observed for FEV(1). Pharmacokinetic evaluation of the peak plasma concentrations and renal excretion suggested no obvious deviation from dose-proportionality over the investigated dose range of 2 μg-40 μg; in most patients, no plasma levels could be detected following the 2 μg dose. All treatments were well tolerated with no apparent dose relation in terms of adverse events.

Conclusions: Olodaterol appears to be a promising long-acting β(2)-adrenoceptor agonist,with bronchodilation maintained over 24 h that offers an opportunity for once-daily dosing in patients who require maintenance bronchodilator therapy for the management of COPD symptoms.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Aged
  • Benzoxazines / adverse effects
  • Benzoxazines / pharmacokinetics
  • Benzoxazines / therapeutic use*
  • Bronchodilator Agents / therapeutic use*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Time Factors


  • Adrenergic beta-2 Receptor Agonists
  • Benzoxazines
  • Bronchodilator Agents
  • olodaterol