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.

• MeSH
• Adrenergic beta-2 Receptor Agonists administration & dosage   adverse effects   pharmacokinetics   MeSH
• Muscarinic Antagonists administration & dosage   adverse effects   pharmacokinetics   MeSH
• Administration, Inhalation MeSH
• Benzyl Alcohols administration & dosage   adverse effects   pharmacokinetics   MeSH
• Bronchodilator Agents administration & dosage   adverse effects   pharmacokinetics   MeSH
• Quinuclidines administration & dosage   adverse effects   pharmacokinetics   MeSH
• Chlorobenzenes administration & dosage   adverse effects   pharmacokinetics   MeSH
• Adult MeSH
• Renal Elimination MeSH
• Drug Combinations MeSH
• Single-Blind Method MeSH
• Middle Aged MeSH
• Humans MeSH
• Kidney Diseases diagnosis   metabolism   MeSH
• Area Under Curve MeSH
• Dry Powder Inhalers MeSH
• Aged MeSH
• Severity of Illness Index MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Controlled Clinical Trial MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Hungary MeSH