title: Model-based evaluation of pulmonary pharmacokinetics in asthmatic and COPD patients after oral olodaterol inhalation.
abstract: Olodaterol is an orally inhaled β2 -agonist for treatment of chronic obstructive pulmonary disease (COPD). The aims of this population pharmacokinetic (PK) analysis were: (1) to investigate systemic PK and thereby make inferences about pulmonary PK in asthmatic patients, COPD patients and healthy volunteers, and (2) to assess whether differences in pulmonary efficacy might be expected based on pulmonary PK characteristics.
  
  
  
  Plasma and urine data after olodaterol inhalation were available from six clinical trials comprising 710 patients and healthy volunteers (single and multiple dosing). To investigate the relevance of covariates, full fixed-effect modelling was applied based on a previously developed healthy volunteer systemic disposition model.
  
  
  
  A pulmonary model with three parallel absorption processes best described PK after inhalation in patients. The pulmonary bioavailable fraction (PBIO) was 48.7% (46.1-51.3%, 95% confidence interval) in asthma, and 53.6% (51.1-56.2%) in COPD. In asthma 87.2% (85.4-88.8%) of PBIO was slowly absorbed with an absorption half-life of 18.5 h (16.3-21.4 h), whereas in COPD 80.1% (78.0-82.2%) was absorbed with a half-life of 37.8 h (31.1-47.8 h). In healthy volunteers absorption was faster, with a half-life of 18.5 h (16.3-21.4 h) of the slowest absorbed process, which characterized 74.6% (69.1-80.2%) of PBIO.
  
  
  
  The modelling approach successfully described data after olodaterol inhalation in patients and healthy volunteers. Slow pulmonary absorption was demonstrated both in asthma and COPD. Absorption characteristics after olodaterol inhalation indicated even more beneficial lung targeting in patients compared to healthy volunteers.
authors.affiliation: Institute of Pharmacy, Department of Clinical Pharmacy and Biochemistry, Freie Universität Berlin, 12169, Berlin, Germany.|Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Jens Markus
authors.initials: JM
authors.lastname: Borghardt
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weber
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Staab
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Kunz
authors.affiliation: Institute of Pharmacy, Department of Clinical Pharmacy and Biochemistry, Freie Universität Berlin, 12169, Berlin, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kloft
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D048588:Benzoxazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D055815:Young Adult
chemical_list: D048588:Benzoxazines; D001993:Bronchodilator Agents; C549647:olodaterol
keywords: COPD; asthma; olodaterol inhalation; pharmacometrics; population pharmacokinetics; pulmonary absorption