التفاصيل البيبلوغرافية
| العنوان: |
Effects of Moderate Hepatic Impairment on the Pharmacokinetic Properties and Tolerability of Umeclidinium and Vilanterol in Inhalational Umeclidinium Monotherapy and Umeclidinium/Vilanterol Combination Therapy: An Open-Label, Nonrandomized Study. |
| المؤلفون: |
Mehta, Rashmi1 rashmi.s.mehta@gsk.com, Hardes, Kelly2, Kelleher, Dennis1, Preece, Andrew2, Tombs, Lee3, Brealey, Noushin2 |
| المصدر: |
Clinical Therapeutics. 2014, Vol. 36 Issue 7, p1016-1027.e2. 14p. |
| مصطلحات موضوعية: |
*ADRENERGIC beta agonists, *PHARMACOKINETICS, *MUSCARINIC antagonists, *BLOOD testing, *COMBINATION drug therapy, *CLINICAL trials, *CONFIDENCE intervals, *DRUG side effects, *GENES, *LIVER diseases, *OBSTRUCTIVE lung diseases, *MEDICAL cooperation, *RESEARCH, *RESEARCH funding, *SAFETY, *DATA analysis software, *DESCRIPTIVE statistics, *THERAPEUTICS |
| مصطلحات جغرافية: |
HUNGARY, SLOVAKIA |
| مستخلص: |
Background: The long-acting muscarinic antagonist umeclidinium (UMEC) is approved as a monotherapy, and in combination with the long-acting ß2-agonist vilanterol (VI), as a once-daily inhaled maintenance bronchodilator therapy for chronic obstructive pulmonary disease in the US and EU; they are not indicated for the treatment of asthma. Preclinical and clinical data suggest that UMEC and VI are predominantly eliminated by the liver. Objectives: The objectives of the study were to evaluate the effects of moderate hepatic impairment on the plasma and urinary pharmacokinetic properties of each drug, and on the tolerability of inhalational UMEC/VI 125/25 μg and UMEC 125 μg . Methods: This open-label, nonrandomized study was conducted in patients with moderate hepatic impairment (Child-Pugh score, 7-9) and in healthy volunteers (control). Patients and volunteers were administered a single dose of UMEC/VI 125/25 μg, and, after a 7- to 14-day washout period, repeat-dose UMEC 125 μg once daily for 7 days. Primary end points were the plasma pharmacokinetic properties of single- and repeat-dose UMEC and VI. Secondary end points were the urinary pharmacokinetic properties of UMEC, and the tolerability of each treatment. Results: All 18 enrolled patients and volunteers (12 men, 6 women; mean age, 53.6 years) completed the study. Mean systemic exposures of UMEC and VI were similar or numerically lower in patients with moderate hepatic impairment compared with those in healthy volunteers, but the differences were not clinically significant. UMEC accumulations with 7-day dosing of UMEC were similar between patients with moderate hepatic impairment and healthy volunteers. UMEC/VI 125/25 μg and UMEC 125 μg were well-tolerated, with no safety concerns identified. Conclusions: The administration of UMEC/VI 125/ 25 μg or UMEC 125 μg in patients with moderate hepatic impairment did not result in clinically relevant increases in UMEC or VI exposures compared with those in healthy volunteers. Based on these findings, no dose adjustment for UMEC/VI or UMEC is warranted in patients with moderate hepatic impairment. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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