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