Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, nonrandomized study
Authors Mehta R, Hardes K, Brealey N, Tombs L, Preece A, Kelleher D
Received 21 May 2014
Accepted for publication 26 August 2014
Published 18 December 2014 Volume 2015:10(1) Pages 15—23
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Richard Russell
Rashmi Mehta,1 Kelly Hardes,2 Noushin Brealey,3 Lee Tombs,4 Andrew Preece,2 Dennis Kelleher1
1Respiratory Medicines Development Center, GSK, Research Triangle Park, NC, USA; 2Clinical Pharmacology Science and Study Operations, 3Respiratory Medicines Development Centre, GSK, Stockley Park, UK; 4Statistics and Programming, Synergy, Slough, Berkshire, UK
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.
Objectives: 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.
Conclusion: 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.
Keywords: chronic obstructive pulmonary disease, exposure, GSK573719, long-acting beta2 agonist, long-acting muscarinic antagonist
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