Effect of severe renal impairment on umeclidinium and umeclidinium/vilanterol pharmacokinetics and safety: a single-blind, nonrandomized study.

ABSTRACT: 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.To evaluate the effect of severe renal impairment on the pharmacokinetics of umeclidinium and umeclidinium/vilanterol.Nine patients with severe renal impairment (creatinine clearance <30 mL/min) and nine matched healthy volunteers received a single dose of umeclidinium 125 ?g; and after a 7- to 14-day washout, a single dose of umeclidinium/vilanterol 125/25 ?g.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 ?g or umeclidinium/vilanterol 125/25 ?g 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 ?g and umeclidinium/vilanterol 125/25 ?g administration, respectively. Treatments were well tolerated in both populations.Umeclidinium 125 ?g or umeclidinium/vilanterol 125/25 ?g 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.

SUBMITTER: Mehta R 

PROVIDER: S-EPMC4279609 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature