title: Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, nonrandomized study.
abstract: BACKGROUND
  Umeclidinium and vilanterol, long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease, are primarily eliminated via the hepatic route; however, severe renal impairment may adversely affect some elimination pathways other than the kidney.
  
  
  OBJECTIVE
  To evaluate the effect of severe renal impairment on the pharmacokinetics of umeclidinium and umeclidinium/vilanterol.
  
  
  METHODS
  Nine patients with severe renal impairment (creatinine clearance <30 mL/min) and nine matched healthy volunteers received a single dose of umeclidinium 125 μg; and after a 7- to 14-day washout, a single dose of umeclidinium/vilanterol 125/25 μg.
  
  
  RESULTS
  No clinically relevant increases in plasma umeclidinium or vilanterol systemic exposure (area under the curve or maximum observed plasma concentration) were observed following umeclidinium 125 μg or umeclidinium/vilanterol 125/25 μg administration. On average, the amount of umeclidinium excreted in 24 hours in urine (90% confidence interval) was 88% (81%-93%) and 89% (81%-93%) lower in patients with severe renal impairment compared with healthy volunteers following umeclidinium 125 μg and umeclidinium/vilanterol 125/25 μg administration, respectively. Treatments were well tolerated in both populations.
  
  
  CONCLUSIONS
  Umeclidinium 125 μg or umeclidinium/vilanterol 125/25 μg administration to patients with severe renal impairment did not demonstrate clinically relevant increases in systemic exposure compared with healthy volunteers. No dose adjustment for umeclidinium and umeclidinium/vilanterol is warranted in patients with severe renal impairment.
authors.affiliation: Respiratory Medicines Development Center, GSK, Research Triangle Park, NC, USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Mehta
authors.affiliation: Clinical Pharmacology Science and Study Operations, GSK, Stockley Park, UK.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hardes
authors.affiliation: Respiratory Medicines Development Centre, GSK, Stockley Park, UK.
authors.forename: Noushin
authors.initials: N
authors.lastname: Brealey
authors.affiliation: Statistics and Programming, Synergy, Slough, Berkshire, UK.
authors.forename: Lee
authors.initials: L
authors.lastname: Tombs
authors.affiliation: Clinical Pharmacology Science and Study Operations, GSK, Stockley Park, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Preece
authors.affiliation: Respiratory Medicines Development Center, GSK, Research Triangle Park, NC, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Kelleher
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002722:Chlorobenzenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018153:Czech Republic; D004338:Drug Combinations; D058995:Dry Powder Inhalers; D005260:Female; D006801:Humans; D006814:Hungary; D007674:Kidney Diseases / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D065667:Renal Elimination; D012720:Severity of Illness Index; D016037:Single-Blind Method
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; D004338:Drug Combinations; C573971:GSK573719; D018727:Muscarinic Antagonists; D011812:Quinuclidines; C550468:vilanterol
keywords: GSK573719; chronic obstructive pulmonary disease; exposure; long-acting beta2 agonist; long-acting muscarinic antagonist