Chuchalin Alexander G, Tsoi Alla N, Richter Kai, Krug Norbert, Dahl Ronald, Luursema P B, Cameron Ray, Bao Weibin, Higgins Mark, Woessner Ralph, van As Andre
Pulmonology Research Institute, Parkovaya Street, 32/61, 105077 Moscow, Russian Federation.
Respir Med. 2007 Oct;101(10):2065-75. doi: 10.1016/j.rmed.2007.06.002. Epub 2007 Jul 20.
The safety and tolerability of indacaterol, a novel once-daily beta(2)-agonist bronchodilator with a fast onset of action, were assessed in 156 asthma patients in a multicentre, randomized, double-blind, placebo-controlled study. Patients received indacaterol 200, 400 or 600 microg or placebo once daily for 28 days. Adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, spirometry and physical examinations were monitored. Indacaterol pharmacokinetics were assessed. There was no evidence of dose-related increases in AE incidence or clinically significant hypokalaemia or hyperglycaemia in indacaterol-treated patients. Mean pulse rate changes were minor in any group, with maximum 1-h post-dose changes from baseline of -3.7, -3.3 and -2.2 bpm for indacaterol 200, 400 and 600 microg, respectively, and -2.9 bpm for placebo. Mean QTc interval was similar between groups; change from baseline >60 ms occurred in only two patients. Mean FEV(1) increased after the first indacaterol dose; baseline-adjusted pre-dose (trough) values remained >or=166 mL higher than placebo at all subsequent visits, supporting a 24-h bronchodilator effect. Pre-dose (but not post-dose) serum indacaterol concentrations indicated a slight trend for accumulation. Once-daily indacaterol 200-600 microg has a favourable therapeutic index. It is well tolerated, and is not associated with any adverse cardiac or metabolic effects, while providing effective 24-h bronchodilation.
茚达特罗是一种新型的每日一次的β₂受体激动剂支气管扩张剂，起效迅速。在一项多中心、随机、双盲、安慰剂对照研究中，对156例哮喘患者评估了茚达特罗的安全性和耐受性。患者每日一次接受200、400或600微克茚达特罗或安慰剂治疗，为期28天。监测不良事件（AE）、实验室检查、生命体征、心电图、肺功能测定和体格检查。评估了茚达特罗的药代动力学。在接受茚达特罗治疗的患者中，没有证据表明不良事件发生率与剂量相关增加，也没有临床显著的低钾血症或高血糖症。任何组的平均脉搏率变化都很小，茚达特罗200、400和600微克组给药后1小时相对于基线的最大变化分别为-3.7、-3.3和-2.2次/分钟，安慰剂组为-2.9次/分钟。各组间平均QTc间期相似；仅2例患者相对于基线的变化>60毫秒。首次给予茚达特罗后，平均第一秒用力呼气量（FEV₁）增加；在所有后续访视中，经基线调整的给药前（谷值）值比安慰剂高≥166毫升，支持24小时支气管扩张作用。给药前（而非给药后）血清茚达特罗浓度显示有轻微的蓄积趋势。每日一次给予200 - 600微克茚达特罗具有良好的治疗指数。它耐受性良好，与任何不良心脏或代谢效应无关，同时提供有效的24小时支气管扩张作用。
