哮喘联盟

   摘要
   试验目的：采用吸入异物的咳嗽反射敏感性测试作为药理终点指标。本研究中，我们将在健康志愿者中比较布他米酯、右美沙芬以及安慰剂对辣椒诱导咳嗽的疗效。
   方法：在随机、空白对照、6组交叉设计的试验中，受试者分别接受30mg右美沙芬，四种剂量的布他米酯及安慰剂治疗，并在基线、服药2、4、6、8、12及24小时后吸入逐渐增量的辣椒素，以评估药物疗效。主要终点指标为给药前至给药12小时，log10 C5的0-12小时曲线下面积。试验还检测了血浆中布他米酯的代谢情况，以评估药代动力学与药效间的关系。
   结果：34名入组患者（13名男性，中位年龄25岁）完成了研究。研究中所有组的咳嗽敏感性均较基线下降。其中右美沙芬疗效优于安慰剂（P=0.01），但45mg最大衰减剂量布他米酯治疗并未体现显著疗效。布他米酯的药代动力学与其药效没有明显关联。
   结论：本试验首次证实右美沙芬可缓解辣椒素引起的咳嗽，明确了其在咳嗽反射中的广泛作用。而布他米酯的疗效欠佳可能是由于高剂量给药带来的配方问题。
 

（刘国梁 审校）
Br J Clin Pharmacol. 2014 Jul 4. doi: 10.1111/bcp.12458. [Epub ahead of print]

 

A randomised placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers.
 

Faruqi S1, Wright C, Thompson R, Morice A.
 

ABSTRACT
AIMS: The examination of cough reflex sensitivity through inhalational challenge can be utilised to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers.
METHODS: In this randomized, placebo-controlled, 6-way cross-over study the effect of dextromethrophan 30 mg, 4 doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2,4,6,8,12 and 24 hours following dosing. The primary endpoint was the Area Under the Curve 0-12h of log10 C5 from pre-dose to 12 hour after dosing. Plasma butamirate metabolites were analysed to evaluate pharmacokinetic and pharmacodynamic relationships.
RESULTS: 34 subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (p=0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate.
CONCLUSIONS: We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses.
 

Br J Clin Pharmacol. 2014 Jul 4. doi: 10.1111/bcp.12458. [Epub ahead of print]