GlaxoSmithKline, Research Triangle Park, NC, USA.
GlaxoSmithKline, Stevenage, Hertfordshire, UK.
J Clin Pharmacol. 2018 Nov;58(11):1461-1467. doi: 10.1002/jcph.1253. Epub 2018 May 15.
A population pharmacokinetic analysis was conducted from a subset of samples obtained from the Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy trial to characterize the pharmacokinetics of fluticasone furoate, umeclidinium, and vilanterol in patients with symptomatic COPD following treatment with fluticason furoate-umeclidinium-vilanterol combined in a single inhaler. This was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticason furoate-umeclidinium-vilanterol, 100 μg/62.5 μg/25 μg; Ellipta inhaler) with twice-daily dual therapy (budesonide/formoterol 400 μg/12 μg; Turbuhaler). The analyses were conducted in a subset of 74 patients who received fluticason furoate-umeclidinium-vilanterol and provided serial or sparse samples. Monte Carlo simulations and a model-based estimation approach both indicated that systemic drug concentrations of fluticasone furoate, umeclidinium, and vilanterol after administration of fluticason furoate-umeclidinium-vilanterol triple combination therapy from a single inhaler were within the ranges observed following administration of these drugs as monotherapy (fluticasone furoate, umeclidinium, and vilanterol) or as dual-combination therapy (fluticasone furoate/vilanterol or umeclidinium/vilanterol).
进行了一项群体药代动力学分析，该分析基于接受三联疗法（氟替卡松富马酸酯-乌美溴铵-维兰特罗，100μg/62.5μg/25μg；Ellipta 吸入器）治疗的患者的亚组样本，这些患者来自慢性阻塞性肺疾病肺功能和生活质量评估的 Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy 试验，以确定有症状的慢性阻塞性肺疾病患者接受氟替卡松富马酸酯-乌美溴铵-维兰特罗三联疗法治疗后氟替卡松富马酸酯、乌美溴铵和维兰特罗的药代动力学特征。这是一项随机、双盲、双模拟研究，比较了每日一次三联疗法（氟替卡松富马酸酯-乌美溴铵-维兰特罗，100μg/62.5μg/25μg；Ellipta 吸入器）与每日两次双药疗法（布地奈德/福莫特罗 400μg/12μg；Turbuhaler）的 24 周治疗效果。该分析在接受氟替卡松富马酸酯-乌美溴铵-维兰特罗三联治疗且提供连续或稀疏样本的 74 例患者的亚组中进行。蒙特卡罗模拟和基于模型的估计方法均表明，从单吸入器给予氟替卡松富马酸酯-乌美溴铵-维兰特罗三联疗法后，氟替卡松富马酸酯、乌美溴铵和维兰特罗的系统药物浓度在这些药物单药治疗（氟替卡松富马酸酯、乌美溴铵和维兰特罗）或双药联合治疗（氟替卡松富马酸酯/维兰特罗或乌美溴铵/维兰特罗）时观察到的范围内。
