哮喘联盟

摘要
   维兰特罗(VI; GW642444M)是一种新型吸入性长效β2受体激动剂，体外活性能持续24 h，常与皮质激素丙酸氟替卡松联合使用治疗COPD和哮喘。在健康受试者、轻度-中度持续性哮喘和中重度COPD患者中，对VI的安全性、耐受性、药代动力学和药效学进行了评价。在哮喘和COPD患者中给予每日1次单剂量VI(25-100 μg) 治疗，并在健康受试者中重复剂量每日1次治疗，治疗持续14天。给药后检测不良反应事件（AE）、生命体征、心电图、药效学终点、FEV1和VI血浆药代动力学（AUC、Cmax和Tmax）。VI (25-100 μg) 能很好耐受。AE的发生率和严重程度均与安慰剂相当。VI给药后，生命体征、12导心电图、Holter心电图、血糖和血钾均无临床显著异常。单剂量和重复剂量VI给药（最高50 μg）对QTc无明显影响。健康受试者100 μg VI单剂量和重复剂量治疗和哮喘患者单剂量治疗后存在某些差异。对于哮喘患者和COPD患者，所有VI治疗均能增加FEV1，该变化最早在给药后5 min即出现，维持至给药后的24 h。对于所有受试者，VI能均快速吸收（健康者：中位Tmax为5 min；哮喘和COPD患者：中位Tmax为10 min），全身VI暴露水平与VI剂量成比例。重复剂量给药后可观察到边际积累。哮喘患者和COPD患者单剂量吸入VI，健康受试者重复剂量吸入VI，均能很好耐受，无全身不良反应。VI能产生快速和持久的支气管舒张作用，作用持续24 h，提示可采用每日1次的给药方式。

                                                                                           (林江涛 审校)
PulmPharmacolTher.2012Dec8.pii:S1094-5539(12)00172-1.doi:10.1016/j.pupt.2012.12.001.[Epub ahead of print]
 

Vilanterol trifenatate, a novel inhaled long-acting beta2 adrenoceptor agonist, is well tolerated in healthy subjects and demonstrates prolonged bronchodilation in subjects with asthma and COPD.

 
Kempsford R, Norris V, Siederer S.

Source
Respiratory & Immuno-Inflammation Medicine Development Centre, GlaxoSmithKline R&D, Stevenage, Hertfordshire SG1 2NY, United Kingdom. Electronic address: rodger.d.kempsford@gsk.com.

Abstract
Vilanterol (VI; GW642444M) is a novel inhaled long-acting β2-agonist with inherent 24 h activity in vitro in development as a combination with the inhaled corticosteroid fluticasone furoate for both COPD and asthma. These studies were conducted to determine the safety, tolerability, pharmacodynamics and pharmacokinetics of VI in healthy subjects and subjects with mild to moderate persistent asthma and moderate to severe COPD. Single doses of VI (25-100 μg) were given once daily to subjects with asthma and COPD and repeat doses once daily for 14 days to healthy subjects. Adverse events (AEs), vital signs, ECGs, pharmacodynamic endpoints, FEV(1) and VI plasma pharmacokinetics (AUC, Cmax and Tmax) were determined following dosing. VI (25-100 μg) was well tolerated. The incidence and severity of AEs were comparable to placebo. Following VI administration there were no clinically significant abnormalities in vital signs, 12-lead ECG, Holter ECG, blood glucose or potassium. There were no statistically significant effects on QTc of single and repeat VI doses up to 50 μg; some differences were seen following the 100 μg VI dose after single and repeat dose in healthy subjects and single dose in asthmatic subjects. All VI doses produced increases in FEV(1) from as early as 5 min after dosing which were maintained up to 24 h post-dose in subjects with asthma and COPD. In all subjects VI was rapidly absorbed (healthy subjects median Tmax at 5 min; asthma and COPD subjects median Tmax at 10 min) with systemic exposure increasing in an approximately dose proportional manner across the VI dose range. Marginal accumulation was seen on repeat dosing. Single doses of inhaled VI in subjects with asthma and COPD and repeat doses in healthy subjects were well tolerated with no clinically significant unwanted systemic effects. VI produced a rapid and prolonged bronchodilation over 24 h suggesting the potential for once daily administration.

Pulm Pharmacol Ther. 2012 Dec 8. pii: S1094-5539(12)00172-1. doi: 10.1016/j.pupt.2012.12.001. [Epub ahead of print]