title: Pharmacokinetics and safety of olodaterol administered with the Respimat Soft Mist inhaler in subjects with impaired hepatic or renal function.
abstract: OBJECTIVE
  In two trials, the influences of hepatic and renal impairment on the pharmacokinetics of olodaterol, a novel long-acting inhaled β2-agonist for treatment of COPD, were investigated.
  
  
  METHODS
  The first trial included eight subjects with mild hepatic function impairment (Child-Pugh A), eight subjects with moderate impairment (Child-Pugh B), and 16 matched healthy subjects with normal hepatic function. The second trial included eight subjects with severe renal impairment (creatinine clearance <30 mL·min(-1)) and 14 matched healthy subjects with normal renal function. Subjects received single doses of 20 or 30 μg olodaterol administered with the Respimat Soft Mist inhaler.
  
  
  RESULTS
  Olodaterol was well tolerated in all subjects. The geometric mean ratios and 90% confidence intervals of dose-normalized area under the plasma concentration-time curve from time zero to 4 hours (AUC0-4) for subjects with mild and moderate hepatic impairment compared to healthy subjects were 97% (75%-125%) and 105% (79%-140%), respectively. Corresponding values for dose-normalized maximum concentration (C max) were 112% (84%-151%) (mild impairment) and 99% (73%-135%) (moderate impairment). The geometric mean ratio (90% confidence interval) of AUC0-4 for subjects with severe renal impairment compared to healthy subjects was 135% (94%-195%), and for C max was 137% (84%-222%). There was no significant relationship between creatinine clearance and AUC0-4 or C max. Renal clearance of olodaterol was reduced to 20% of normal in severe renal impairment.
  
  
  CONCLUSIONS
  Mild to moderate hepatic function impairment or severe renal function impairment did not result in a clinically relevant increase of olodaterol systemic exposure after a single inhaled dose.
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Kunz
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany.
authors.forename: Doreen
authors.initials: D
authors.lastname: Luedtke
authors.affiliation: Global Biometrics and Clinical Applications, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Unseld
authors.affiliation: Boehringer Ingelheim, Burlington, ON, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Hamilton
authors.affiliation: CRS Clinical Research Services Kiel GmbH, Kiel, Germany.
authors.forename: Atef
authors.initials: A
authors.lastname: Halabi
authors.affiliation: Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Wein
authors.affiliation: Medicine Coordination, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Formella
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000150:complications*; D008107:Liver Diseases / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D048588:Benzoxazines; C549647:olodaterol
keywords: chronic obstructive pulmonary disease; exposure; hepatic impairment; long-acting β2-agonist; olodaterol; renal impairment